Total submissions: 5272
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001796951 | SCV002037592 | likely benign | Mitochondrial disease | 2021-10-26 | reviewed by expert panel | curation | The m.10172G>A (p.E38E) variant in MT-ND3 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is seen in over 0.8% of individuals in the GenBank dataset (BS1), including in haplogroups J2b (97.91% of individuals), U6a (7.44% of individuals), Q1f (10/17 individuals), and M13b (7/13 individuals). Furthermore, this variant is seen in the gnomAD dataset (v3.1.2) at an overall homoplasmic allele frequency of 0.58% including in haplogroup J at 6.7%. If an affected individual is not a member of one of these haplogroups, further evaluation of the variant in that particular individual should be considered. This is a synonymous variant (BP7). In summary, this variant meets criteria to be classified as likely benign given its synonymous nature and high frequency in the general population. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BS1, BP7. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029934 | SCV000052589 | likely pathogenic | Maturity-onset diabetes of the young, type 2 | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
| Developmental Genetics Unit, |
RCV000171541 | SCV000221740 | likely pathogenic | not provided | criteria provided, single submitter | research | ||
| Eurofins NTD LLC |
RCV000178410 | SCV000230484 | uncertain significance | not provided | 2014-10-03 | criteria provided, single submitter | clinical testing | |
| Dobyns Lab, |
RCV000191932 | SCV000246158 | pathogenic | Poretti-Boltshauser syndrome | 2014-11-25 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000210429 | SCV000256763 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive | 2014-07-16 | criteria provided, single submitter | research | segregates with the phenotype in an affected family |
| Oxford Medical Genetics Laboratories, |
RCV000210049 | SCV000257461 | pathogenic | Combined immunodeficiency due to DOCK8 deficiency | 2015-08-25 | criteria provided, single submitter | clinical testing | |
| Lupski Lab, |
RCV000203452 | SCV000258328 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203475 | SCV000258329 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203496 | SCV000258330 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203458 | SCV000258331 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203474 | SCV000258332 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203463 | SCV000258334 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203486 | SCV000258335 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203462 | SCV000258337 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203484 | SCV000258338 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203447 | SCV000258339 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203468 | SCV000258340 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203483 | SCV000258341 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203451 | SCV000258342 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203466 | SCV000258343 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203489 | SCV000258344 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203456 | SCV000258345 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203472 | SCV000258346 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203499 | SCV000258350 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203453 | SCV000258351 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203460 | SCV000258354 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203481 | SCV000258355 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203495 | SCV000258356 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203464 | SCV000258357 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203480 | SCV000258358 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203449 | SCV000258359 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203485 | SCV000258361 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203448 | SCV000258362 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203469 | SCV000258363 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203491 | SCV000258364 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203459 | SCV000258365 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203467 | SCV000258366 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203490 | SCV000258367 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203473 | SCV000258369 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203488 | SCV000258370 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203492 | SCV000258373 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203498 | SCV000258376 | pathogenic | Spastic paraplegia 4, autosomal dominant | 2014-08-07 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203289 | SCV000258388 | likely pathogenic | Bosch-Boonstra-Schaaf optic atrophy syndrome | 2014-02-06 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000203294 | SCV000258389 | likely pathogenic | Bosch-Boonstra-Schaaf optic atrophy syndrome | 2014-02-06 | criteria provided, single submitter | research | |
| Baylor Genetics | RCV000240814 | SCV000258399 | pathogenic | Cholestasis, progressive familial intrahepatic 1 | 2015-12-17 | criteria provided, single submitter | clinical testing | This variant was found in compound heterozygous status with another pathogenic insertion variant in two affected members of a Caucasian family |
| Lupski Lab, |
RCV000210394 | SCV000258457 | pathogenic | Chromosome 17p13.1 deletion syndrome | 2015-11-06 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000210404 | SCV000258458 | pathogenic | Chromosome 17p13.1 deletion syndrome | 2015-11-06 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000210387 | SCV000258459 | pathogenic | Chromosome 17p13.1 deletion syndrome | 2015-11-06 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000210397 | SCV000258460 | pathogenic | Chromosome 17p13.1 deletion syndrome | 2015-11-06 | criteria provided, single submitter | research | |
| Ludwig Lab, |
RCV000417195 | SCV000262654 | likely pathogenic | Currarino triad | criteria provided, single submitter | research | Large de novo duplication in a patient with negative family history. | |
| Elsea Laboratory, |
RCV000455872 | SCV000264470 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000454803 | SCV000264471 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000455222 | SCV000264472 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000455812 | SCV000264473 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000454759 | SCV000264474 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000477897 | SCV000264477 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000454618 | SCV000264478 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000477751 | SCV000264479 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Elsea Laboratory, |
RCV000455254 | SCV000264480 | pathogenic | MBD5 associated neurodevelopmental disorder | 2012-10-01 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000210384 | SCV000266398 | pathogenic | Immunodeficiency 23 | 2014-07-03 | criteria provided, single submitter | research | segregates with the phenotype in an affected family |
| Baylor- |
RCV000210452 | SCV000266536 | pathogenic | Loeys-Dietz syndrome 4 | criteria provided, single submitter | research | ||
| Baylor- |
RCV000210464 | SCV000266537 | pathogenic | Loeys-Dietz syndrome 4 | criteria provided, single submitter | research | ||
| Lupski Lab, |
RCV000488894 | SCV000267603 | pathogenic | not provided | 2016-04-26 | criteria provided, single submitter | research | compound heterozygous deletion identified in patient with congenital cataract, seizures, cerebellar and brainstem hypoplasia |
| Lupski Lab, |
RCV000488906 | SCV000267604 | pathogenic | not provided | 2016-04-26 | criteria provided, single submitter | research | compound heterozygous deletion identified in patient with congenital cataract, seizures, cerebellar and brainstem hypoplasia |
| Center for Pediatric Genomic Medicine, |
RCV000224569 | SCV000281025 | uncertain significance | not provided | 2015-12-22 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
| Geschwind lab, |
RCV000225569 | SCV000282087 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225670 | SCV000282088 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225439 | SCV000282089 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225548 | SCV000282090 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225681 | SCV000282091 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225457 | SCV000282092 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225542 | SCV000282093 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225679 | SCV000282094 | likely pathogenic | Autism spectrum disorder | criteria provided, single submitter | research | ||
| Geschwind lab, |
RCV000225451 | SCV000282095 | likely pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225595 | SCV000282096 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225368 | SCV000282097 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225469 | SCV000282098 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225572 | SCV000282099 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225402 | SCV000282100 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225508 | SCV000282101 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225645 | SCV000282102 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225379 | SCV000282103 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225522 | SCV000282104 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225625 | SCV000282105 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance. |
| Geschwind lab, |
RCV000225436 | SCV000282106 | likely pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225546 | SCV000282107 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225619 | SCV000282108 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225434 | SCV000282109 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225539 | SCV000282110 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225676 | SCV000282111 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225448 | SCV000282112 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225559 | SCV000282113 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225649 | SCV000282114 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225471 | SCV000282115 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225587 | SCV000282116 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225404 | SCV000282117 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225463 | SCV000282118 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225607 | SCV000282119 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225377 | SCV000282120 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225525 | SCV000282121 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225621 | SCV000282122 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225398 | SCV000282123 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225516 | SCV000282124 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225620 | SCV000282125 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225430 | SCV000282126 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225540 | SCV000282127 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225633 | SCV000282128 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225410 | SCV000282129 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225556 | SCV000282130 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225671 | SCV000282131 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225446 | SCV000282132 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225549 | SCV000282133 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225687 | SCV000282134 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225459 | SCV000282135 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225604 | SCV000282136 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225659 | SCV000282137 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance. |
| Geschwind lab, |
RCV000225479 | SCV000282138 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225596 | SCV000282139 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225373 | SCV000282140 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225512 | SCV000282141 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225576 | SCV000282142 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225386 | SCV000282143 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225492 | SCV000282144 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225630 | SCV000282145 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225408 | SCV000282146 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance. |
| Geschwind lab, |
RCV000225528 | SCV000282147 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance. |
| Geschwind lab, |
RCV000225629 | SCV000282148 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225442 | SCV000282149 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225550 | SCV000282150 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225685 | SCV000282151 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225421 | SCV000282158 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225563 | SCV000282159 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225663 | SCV000282160 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225455 | SCV000282161 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225599 | SCV000282162 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225655 | SCV000282163 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225476 | SCV000282164 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225574 | SCV000282165 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225391 | SCV000282166 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225489 | SCV000282167 | likely pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225609 | SCV000282168 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225382 | SCV000282169 | pathogenic | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225526 | SCV000282170 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225626 | SCV000282171 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225438 | SCV000282172 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225497 | SCV000282173 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225644 | SCV000282174 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225420 | SCV000282175 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225541 | SCV000282176 | association | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225635 | SCV000282177 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225416 | SCV000282178 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225562 | SCV000282179 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225652 | SCV000282180 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225468 | SCV000282181 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225537 | SCV000282182 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225674 | SCV000282183 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225465 | SCV000282184 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225606 | SCV000282185 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225383 | SCV000282186 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Geschwind lab, |
RCV000225486 | SCV000282187 | uncertain significance | Autism spectrum disorder | 2015-10-12 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000234859 | SCV000291989 | pathogenic | Syndromic X-linked intellectual disability Lubs type | 2015-03-13 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000234878 | SCV000291990 | pathogenic | Syndromic X-linked intellectual disability Lubs type | 2015-03-13 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000234882 | SCV000291993 | pathogenic | Blepharophimosis; Absent speech; Thick lower lip vermilion; Thin upper lip vermilion; Long eyelashes; Intellectual disability, moderate | 2014-03-27 | criteria provided, single submitter | clinical testing | |
| Lupski Lab, |
RCV000235056 | SCV000292303 | pathogenic | Spondylocostal dysostosis 5 | 2015-11-15 | criteria provided, single submitter | research | This variant was observed in 17 individuals with vertebral malformations and rib abnormalities. In each case it was found to be in trans with a high-risk TBX6 haplotype, T-C-A (rs2289292, rs3809624, rs3809627). |
| Lupski Lab, |
RCV000235073 | SCV000292310 | likely pathogenic | Progressive myoclonus epilepsy with ataxia | 2015-09-17 | criteria provided, single submitter | research | This deletion was identified in a patient with seizures and neuropathy. There was no evidence of the deletion in parental samples, indicating that the CNV likely arose de novo in the patient. There are reports in the literature of heterozygous mutations in PRICKLE1 in patients with seizures (PMID: 21276947). The patient also has a de novo heterozygous variant in MFN2. |
| Lupski Lab, |
RCV000235059 | SCV000292312 | likely pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 2015-09-17 | criteria provided, single submitter | research | This duplication was identified in a patient with peripheral neuropathy. There is a report in the literature of MPZ duplication in an individual with peripheral neuropathy (PMID:21787890). |
| Lupski Lab, |
RCV000235046 | SCV000292314 | uncertain significance | Peripheral neuropathy | 2015-09-17 | criteria provided, single submitter | research | This deletion was identified in an individual with peripheral neuropathy. There is no association in the literature between KIF24 and neuropathy. This individual also has an MFN2 pathogenic variant. |
| Lupski Lab, |
RCV000235057 | SCV000292315 | likely pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 2015-09-17 | criteria provided, single submitter | research | This deletion was identified in an individual with peripheral neuropathy. |
| Lupski Lab, |
RCV000235080 | SCV000292316 | pathogenic | Smith-Magenis syndrome | 2015-11-12 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000235042 | SCV000292317 | pathogenic | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 | 2015-11-12 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000235066 | SCV000292340 | pathogenic | Chromosome Xq26.3 duplication syndrome | 2015-11-12 | criteria provided, single submitter | research | XLAG is a newly described condition, which is rare and the phenotype is incompletely characterized, particularly in terms of clinical responses to treatment. The aim of this study was to clinically characterize X-LAG in an expanded cohort of 18 affected patients. |
| Lupski Lab, |
RCV000235052 | SCV000292363 | pathogenic | Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract | 2015-08-18 | criteria provided, single submitter | research | This copy number variation has been previously reported as disease-causing and was identified in a family with PHARC. |
| Eurofins NTD LLC |
RCV000385479 | SCV000330986 | likely benign | not specified | 2015-09-29 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000299568 | SCV000331783 | uncertain significance | not provided | 2016-01-28 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000318149 | SCV000334678 | uncertain significance | not provided | 2015-08-27 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000273531 | SCV000335444 | uncertain significance | not provided | 2015-09-15 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000337319 | SCV000336997 | likely pathogenic | not provided | 2015-10-26 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000400412 | SCV000340516 | pathogenic | not provided | 2016-03-18 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000349357 | SCV000340741 | uncertain significance | not provided | 2016-04-15 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000309059 | SCV000340769 | likely benign | not specified | 2016-04-03 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000299738 | SCV000341602 | uncertain significance | not provided | 2016-05-09 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000308584 | SCV000341702 | uncertain significance | not provided | 2016-05-18 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000315072 | SCV000341808 | uncertain significance | not provided | 2016-06-07 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000278127 | SCV000341988 | uncertain significance | not provided | 2016-05-10 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000340414 | SCV000343758 | uncertain significance | not provided | 2016-07-12 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000292125 | SCV000344235 | benign | not specified | 2016-08-08 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000393096 | SCV000483466 | likely benign | Myopathy, distal, 1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000304800 | SCV000483467 | likely benign | Myosin storage myopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000341222 | SCV000483468 | likely benign | Scapuloperoneal myopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000393119 | SCV000483469 | likely benign | Cardiomyopathy, left ventricular noncompaction | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000310759 | SCV000483470 | likely benign | Dilated Cardiomyopathy, Dominant | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000365436 | SCV000483471 | likely benign | Hypertrophic cardiomyopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000261807 | SCV000483973 | likely benign | Myosclerosis, autosomal recessive | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000330899 | SCV000483974 | likely benign | Collagen VI-related myopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Robarts Research Institute, |
RCV000408813 | SCV000484813 | likely pathogenic | Familial hypercholesterolemia 1 | criteria provided, single submitter | clinical testing | ||
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000414385 | SCV000490158 | pathogenic | Breast-ovarian cancer, familial 2 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000413848 | SCV000490160 | pathogenic | Breast-ovarian cancer, familial 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000414056 | SCV000490166 | pathogenic | Breast-ovarian cancer, familial 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000414007 | SCV000490172 | pathogenic | Breast-ovarian cancer, familial 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000413482 | SCV000490174 | pathogenic | Breast-ovarian cancer, familial 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000414360 | SCV000490175 | pathogenic | Breast-ovarian cancer, familial 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Centre for Mendelian Genomics, |
RCV000414960 | SCV000492733 | pathogenic | Renal cyst; Pancreatic cysts | 2015-09-23 | criteria provided, single submitter | clinical testing | |
| Lupski Lab, |
RCV000415472 | SCV000493131 | likely pathogenic | Chromosome Xq26.3 duplication syndrome | 2016-01-01 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000415468 | SCV000493132 | likely pathogenic | Chromosome Xq26.3 duplication syndrome | 2016-01-01 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000415470 | SCV000493133 | likely pathogenic | Chromosome Xq26.3 duplication syndrome | 2016-01-01 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000415471 | SCV000493134 | likely pathogenic | Chromosome Xq26.3 duplication syndrome | 2016-01-01 | criteria provided, single submitter | research | |
| Lupski Lab, |
RCV000520873 | SCV000494285 | pathogenic | Prader-Willi syndrome | criteria provided, single submitter | research | This deletion of 15q11q13 is de novo and represents the typical recurrent type 2 deletion. | |
| Neurogenetics Laboratory - |
RCV000416971 | SCV000494569 | pathogenic | Epileptic encephalopathy | 2016-11-16 | criteria provided, single submitter | clinical testing | |
| Center for Pediatric Genomic Medicine, |
RCV000426541 | SCV000510962 | uncertain significance | not provided | 2017-01-02 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
| Center for Pediatric Genomic Medicine, |
RCV000426740 | SCV000511008 | uncertain significance | not provided | 2017-01-16 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
| Knight Diagnostic Laboratories, |
RCV000454279 | SCV000538074 | pathogenic | Hypoparathyroidism-retardation-dysmorphism syndrome | 2016-04-08 | criteria provided, single submitter | clinical testing | The heterozygous deletion of exons 3 and 4 that was detected by a single copy loss of 16 oligonucleotide probes spanning approximately 7,842 bp in the TBCE gene, Hg19 chr1: g.(235575072_235577473)_(235582954_235583424)del (NM_ 003193) has not been previously reported in an affected individual. TBCE is the only gene implicated in HRD and suggests that this disorder has a single gene etiology. The out-of-frame deletion leads to premature protein truncation. Deletions and truncation variants are common mechanisms of disease; the c.155-166del12 in the TBCE gene is considered the most common pathogenic variant for this condition (Kerkeni E et al., 2015). Based on these criteria, this CNV is interpreted at pathogenic. We have confirmed the findings using a custom exon-centric microarray. |
| Knight Diagnostic Laboratories, |
RCV000454326 | SCV000538075 | likely pathogenic | Infantile nephronophthisis | 2016-04-19 | criteria provided, single submitter | clinical testing | A heterozygous deletion of the 5’-UTR and exons 1 and 2 was detected by a single copy loss of 117 oligonucleotide probes spanning approximately 139,883 bp in the INVS gene, Hg19 chr9: g.( 102814578_102860399)_(102967421_102968415)del (NM_ 001318381). This variant has not been previously reported in an affected individual. Exon 2, which is deleted in this CNV, contains the start codon, implying a loss of the initiation codon. Several frameshift and nonsense variants in this gene have been described in affected individuals (Tory K et al., 2009) suggesting that loss of functions is mechanism of disease. Based on these criteria, this CNV is interpreted at Likely Pathogenic. We have confirmed the findings using a custom exon-centric microarray. |
| Knight Diagnostic Laboratories, |
RCV000454211 | SCV000538076 | likely pathogenic | Fanconi anemia, complementation group A | 2016-04-01 | criteria provided, single submitter | clinical testing | The c.1627-?_2778+?del deletion in the FANCA gene is novel, however, similar sized deletions in the same genomic vicinity have been previously reported as pathogenic (deletion of exons 18-25: Moghrabi et al. 2009) (deletion of exons 21-29: Castella et al., 2011). Mutations in the coding region of FANCA account for approximately 60-70% of Fanconi Anemia Complementation Group A (FA-A) patients, and approximately 10% of pathogenic mutations are large, multi-exonic deletions (Castella et al., 2011). This deletion encompasses amino acids 543-926 in the FANCA protein, and removes a portion of the BRCA-interacting region (amino acids 740-1083) as well as three important phosphoserines (amino acids 849, 850 and 858) (Folias et al., 2002). In addition, this deletion also disrupts a known nuclear export sequence (amino acids 860-880), which would effectively abolish protein transport from the nucleus to the cytoplasm (Ferrer et al., 2005). Therefore, this novel 11-exon deletion is expected to severely truncate the FANCA protein and compromise its function. The collective evidence supports the classification of the c.1627-?_2778+?del as a recessive likely pathogenic variant for Fanconi Anemia, Complementation Group A. |
| Knight Diagnostic Laboratories, |
RCV000454303 | SCV000538077 | likely pathogenic | Fanconi anemia, complementation group A | 2016-04-01 | criteria provided, single submitter | clinical testing | The c.1627-?_2778+?del deletion in the FANCA gene is novel, however, similar sized deletions in the same genomic vicinity have been previously reported as pathogenic (deletion of exons 18-25: Moghrabi et al. 2009) (deletion of exons 21-29: Castella et al., 2011). Mutations in the coding region of FANCA account for approximately 60-70% of Fanconi Anemia Complementation Group A (FA-A) patients, and approximately 10% of pathogenic mutations are large, multi-exonic deletions (Castella et al., 2011). This deletion encompasses amino acids 543-926 in the FANCA protein, and removes a portion of the BRCA-interacting region (amino acids 740-1083) as well as three important phosphoserines (amino acids 849, 850 and 858) (Folias et al., 2002). In addition, this deletion also disrupts a known nuclear export sequence (amino acids 860-880), which would effectively abolish protein transport from the nucleus to the cytoplasm (Ferrer et al., 2005). Therefore, this novel 11-exon deletion is expected to severely truncate the FANCA protein and compromise its function. The collective evidence supports the classification of the c.1627-?_2778+?del as a recessive likely pathogenic variant for Fanconi Anemia, Complementation Group A. |
| Herman Laboratory, |
RCV000490618 | SCV000579289 | pathogenic | PTEN hamartoma tumor syndrome | 2017-03-01 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000496588 | SCV000579478 | pathogenic | Spinal muscular atrophy, type II; Kugelberg-Welander disease; Werdnig-Hoffmann disease; Spinal muscular atrophy, type IV | 2016-11-08 | criteria provided, single submitter | clinical testing | |
| Yang An- |
RCV000504607 | SCV000583426 | pathogenic | Breast neoplasm | criteria provided, single submitter | clinical testing | ||
| Counsyl | RCV000499484 | SCV000590824 | pathogenic | alpha Thalassemia | 2015-01-14 | criteria provided, single submitter | clinical testing | -α3.7 is classified as an alpha+ mutation. |
| Department of Pathology and Laboratory Medicine, |
RCV000500763 | SCV000590971 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2012-07-10 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000502731 | SCV000590975 | uncertain significance | not specified | criteria provided, single submitter | clinical testing | ||
| Department of Pathology and Laboratory Medicine, |
RCV000500209 | SCV000590979 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2016-10-14 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000504485 | SCV000590987 | pathogenic | Lynch syndrome | 2016-02-05 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000503082 | SCV000590992 | pathogenic | Lynch syndrome | criteria provided, single submitter | clinical testing | ||
| Department of Pathology and Laboratory Medicine, |
RCV000499720 | SCV000590993 | pathogenic | Lynch syndrome | criteria provided, single submitter | clinical testing | ||
| Department of Pathology and Laboratory Medicine, |
RCV000499564 | SCV000590996 | pathogenic | Lynch syndrome | criteria provided, single submitter | clinical testing | ||
| Department of Pathology and Laboratory Medicine, |
RCV000501388 | SCV000590997 | pathogenic | Lynch syndrome | 2015-05-20 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000503363 | SCV000591001 | pathogenic | Lynch syndrome | criteria provided, single submitter | clinical testing | ||
| Department of Pathology and Laboratory Medicine, |
RCV000500604 | SCV000591002 | pathogenic | Lynch syndrome | 2014-01-30 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000502402 | SCV000591003 | pathogenic | Lynch syndrome | 2013-01-18 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000504163 | SCV000591004 | likely pathogenic | Lynch syndrome | 2016-08-05 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000500987 | SCV000591008 | pathogenic | Autosomal recessive polycystic kidney disease | 2016-07-27 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000504539 | SCV000591010 | pathogenic | Autosomal recessive polycystic kidney disease | 2016-07-29 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000500855 | SCV000591011 | likely pathogenic | Lynch syndrome | 2014-12-11 | criteria provided, single submitter | clinical testing | |
| Center of Genomic medicine, |
RCV000500418 | SCV000598154 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2016-08-04 | criteria provided, single submitter | clinical testing | |
| Cardiovascular Research Group, |
RCV000505253 | SCV000599309 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
| Cardiovascular Research Group, |
RCV000505214 | SCV000599316 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
| Cardiovascular Research Group, |
RCV000505243 | SCV000599317 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
| Cardiovascular Research Group, |
RCV000505182 | SCV000599318 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
| Cardiovascular Research Group, |
RCV000505219 | SCV000599319 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
| Cardiovascular Research Group, |
RCV000505246 | SCV000599320 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
| Institute of Human Genetics, |
RCV000505401 | SCV000599662 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2013-11-06 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000505435 | SCV000599703 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2017-08-31 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000506174 | SCV000605444 | uncertain significance | not specified | 2017-03-10 | criteria provided, single submitter | clinical testing | |
| Department of Medical Genetics, |
RCV000506461 | SCV000605722 | likely pathogenic | Breast-ovarian cancer, familial 1 | 2016-01-25 | criteria provided, single submitter | clinical testing | Heterozygous deletion of exon 10 (also known as exon 11) |
| Fundacion Hipercolesterolemia Familiar | RCV000509444 | SCV000607397 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Fundacion Hipercolesterolemia Familiar | RCV000509098 | SCV000607398 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Fundacion Hipercolesterolemia Familiar | RCV000509204 | SCV000607427 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Fundacion Hipercolesterolemia Familiar | RCV000509145 | SCV000607447 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Fundacion Hipercolesterolemia Familiar | RCV000509345 | SCV000607700 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Fundacion Hipercolesterolemia Familiar | RCV000509291 | SCV000607711 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Undiagnosed Diseases Network, |
RCV000551008 | SCV000622149 | uncertain significance | Brown-Vialetto-Van Laere syndrome 1 | 2016-03-02 | criteria provided, single submitter | clinical testing | Clinically diagnosed with riboflavin transporter deficiency; patient responded to high dose vitamin B2 treatment. |
| Invitae | RCV000548818 | SCV000623513 | uncertain significance | Hypertrophic cardiomyopathy | 2018-06-28 | criteria provided, single submitter | clinical testing | A gross duplication of the genomic region encompassing the full coding sequence of the TNNI3 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with a TNNI3-related disease. In summary, the exact genomic location of this variant is unknown and the effect of this whole TNNI3 gene duplication is unknown. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000549634 | SCV000623932 | pathogenic | Primary ciliary dyskinesia | 2017-04-23 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exon 9 of the CCDC39 gene. While the exact position of the duplicated exon cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a CCDC39-related disease. However, it has been observed with a pathogenic variant (c.610-2A>G) in CCDC39 in an individual with primary ciliary dyskinesia (Invitae). While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests that the duplication of this exon may contribute to the cause of disease. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV000539192 | SCV000623934 | pathogenic | Primary ciliary dyskinesia | 2017-08-11 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 54-70 of the DNAH5 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. This duplication has not been reported in the literature in individuals with DNAH5-related disease. However, it has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with primary ciliary dyskinesia (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV000527667 | SCV000623936 | likely pathogenic | Primary ciliary dyskinesia | 2017-02-06 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 7-14 of the DNAH11 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. A copy number variant encompassing the same exons of DNAH11 occurs with a second rare variant (p.Arg3429Ser) in an individual with primary ciliary dyskinesia (PMID:26139845). While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests a duplication of exons 7-14 may contribute to the cause of disease. In summary, this variant is a rare exon level duplication, and a similar copy number variant has been reported in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV000531596 | SCV000624563 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2017-04-11 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 1-4 of the MSH2 gene. If EPCAM has been tested and no copy number events are reported for it, then the 5' boundary of this event lies between the EPCAM and MSH2 genes. If EPCAM has not been tested, the 5' end of this event is unknown as it extends beyond the assayed region of this test. The 3' boundary is likely confined to intron 4 of the MSH2 gene. This duplication has not been reported in the literature in individuals with an MSH2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on MSH2 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000544514 | SCV000624570 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-03-29 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exons 5-7 of the MSH2 gene. While the exact position of this variant cannot be determined from this data, sub-genic copy number gains are generally in tandem (PMID: 25640679) and may result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for MSH2 duplications of exons 5-7 (Variation ID: 218047). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV000542078 | SCV000624598 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2017-02-13 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 6-14 of the PMS2 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals with a PMS2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on PMS2 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000544111 | SCV000625805 | uncertain significance | Duchenne muscular dystrophy | 2017-08-08 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exon 30 of the DMD gene. While the exact position of the duplicated exon cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals with DMD-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000547407 | SCV000625808 | pathogenic | Duchenne muscular dystrophy | 2017-07-19 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 2-18 of the DMD gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. Duplication of exons 2-18 has not been reported in the literature in individuals with DMD-related disease. Sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV000546533 | SCV000626134 | uncertain significance | Fanconi anemia | 2017-06-23 | criteria provided, single submitter | clinical testing | A gross duplication of the genomic region encompassing the full coding sequence of the FANCG gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with a FANCG-related disease. The exact genomic location of this variant is unknown. In summary, this variant has uncertain impact on FANCG function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000529549 | SCV000628836 | uncertain significance | Neurofibromatosis, type 2 | 2017-05-02 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 13-16 of the NF2 gene. The 5' boundary is likely confined to intron 12. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with a NF2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on NF2 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000557921 | SCV000629385 | uncertain significance | Spastic paraplegia | 2017-03-21 | criteria provided, single submitter | clinical testing | A gross duplication of the genomic region encompassing the full coding sequence of the HSPD1 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with a HSPD1-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on HSPD1 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000550770 | SCV000630741 | uncertain significance | Hereditary pancreatitis | 2017-07-07 | criteria provided, single submitter | clinical testing | A gross duplication of the genomic region encompassing the full coding sequence of the SPINK1 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with SPINK1-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000554640 | SCV000631437 | uncertain significance | Ehlers-Danlos syndrome, classic type | 2017-02-12 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 8-54 of the COL5A2 gene. The 5' boundary is likely confined to intron 7. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes . As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. Duplications of exons 8-54  sequence have not been reported in the literature in individuals with a COL5A2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on COL5A2 protein function has not been established. Therefore, it has been classified as a Variant of Unknown Significance. |
| Invitae | RCV000527946 | SCV000632906 | likely pathogenic | Familial cancer of breast | 2017-11-03 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 2-3 of the BARD1 gene. While the exact position of the duplicated exons cannot be determined from this data, sub-genic duplications are generally in tandem (PMID: 25640679) and may result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BARD1-related disease. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV000529270 | SCV000633748 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2017-07-21 | criteria provided, single submitter | clinical testing | This copy number variant is a gain (6 copies) of the genomic region encompassing exon 8 of the HCN1 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copies of this region are likely in tandem and in-frame, therefore preserving the integrity of the reading frame. Similar copy number gains have not been reported in the literature in individuals with HCN1-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000557636 | SCV000635101 | likely pathogenic | Hereditary breast and ovarian cancer syndrome | 2017-03-21 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 12-13 of the BRCA2 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). In summary, sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. However, the exact location of this duplication has not been confirmed. Therefore, it has been classified as Likely Pathogenic. |
| Invitae | RCV000545391 | SCV000636113 | benign | Nephronophthisis | 2017-02-10 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000534213 | SCV000638448 | uncertain significance | Neuronopathy, distal hereditary motor, type viia; Myasthenic syndrome, congenital, 20, presynaptic | 2017-07-05 | criteria provided, single submitter | clinical testing | A gross duplication of the genomic region encompassing the full coding sequence of the SLC5A7 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This duplication has not been reported in the literature in individuals with SLC5A7-related disease. Experimental studies are not available for this duplication and the functional significance of an additional copy of this gene is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000528877 | SCV000638530 | uncertain significance | Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Intellectual disability, autosomal dominant 9 | 2016-09-23 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 38 to 46 of the KIF1A gene. The 5' boundary is likely confined to intron 37. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with a KIF1A-related disease, and its frequency in the general population is not known. In summary, because the exact 3' boundary of this variant has not been determined, and whether this duplication occurs in tandem is not known, the impact of this duplication on KIF1A protein function can not be established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000534639 | SCV000638531 | benign | Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Intellectual disability, autosomal dominant 9 | 2018-01-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000540097 | SCV000642053 | likely benign | Hereditary motor and sensory neuropathy, Okinawa type; Spastic paraplegia 57, autosomal recessive | 2017-12-29 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000530985 | SCV000642208 | uncertain significance | Spastic paraplegia 11, autosomal recessive | 2018-03-14 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 31-32 of the SPG11 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. Duplications of exons 31-32 have not been reported in the literature in individuals with a SPG11-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on SPG11 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000538692 | SCV000644700 | likely pathogenic | Cerebral cavernous malformation | 2017-04-18 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 7-9 of the KRIT1 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. This variant  has not been reported in the literature in individuals with a KRIT1-related disease. In summary, sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. However, the exact location of this duplication has not been confirmed. Therefore, it has been classified as Likely Pathogenic. |
| Invitae | RCV000543941 | SCV000646080 | uncertain significance | Progressive familial heart block type IB | 2018-01-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000534711 | SCV000647150 | likely pathogenic | Familial adenomatous polyposis 1 | 2017-02-17 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 2-4 of the APC gene. The 5' end of this event is likely confined to intron 1 of the APC gene. The 3' boundary is likely confined to intron 4 of the APC gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. While this particular duplication has not been reported in the literature, loss-of-function variants including gross alterations in APC are known to be pathogenic (PMID: 23159591). In summary, sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. However, the exact location of this duplication has not been confirmed. Therefore, it has been classified as Likely Pathogenic. |
| Invitae | RCV000548052 | SCV000648588 | uncertain significance | Neuroblastoma 3 | 2017-04-10 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 5 to 29 of the ALK gene. The 5' boundary is likely confined to intron 4. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with an ALK-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on ALK protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000547325 | SCV000650689 | uncertain significance | Idiopathic Pulmonary Fibrosis; Dyskeratosis congenita, autosomal dominant, 2 | 2017-03-30 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 7-16 of the TERT gene. The 5' boundary is likely confined to intron 6. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This gross duplication has not been reported in the literature in an individual with TERT-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on TERT protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance |
| Invitae | RCV000527830 | SCV000650882 | uncertain significance | Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant | 2017-01-24 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exon 47 of the FLNC gene. While the exact position of the duplicated exon cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. This variant has not been reported in the literature in an individual with a FLNC-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on FLNC protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000550477 | SCV000652333 | pathogenic | Epileptic encephalopathy, early infantile, 1; Spinocerebellar ataxia, autosomal recessive 12 | 2017-07-21 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing most of exon 6 of the WWOX gene, including the intron 5-exon 6 boundary (c.517-68114_597dup). The duplicated copy of this region is in tandem. This likely creates a premature translational stop signal and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in WWOX are known to be pathogenic (PMID: 25411445). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV000552669 | SCV000652820 | uncertain significance | Spinal muscular atrophy, distal, autosomal recessive, 5 | 2017-06-05 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exon 10 of the DNAJB2 gene. The 5' boundary is likely confined to intron 9. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes.  There is evidence that this duplication is in tandem. This duplication has not been reported in the literature in individuals with a DNAJB2-related disease. Experimental studies are not available for this copy number variant, and the functional significance of the duplicated exon is currently unknown. In summary, this is a tandem duplication with uncertain impact on DNAJB2 function.  The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000552282 | SCV000652857 | uncertain significance | Joubert syndrome 20; Meckel syndrome, type 11 | 2017-06-07 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 4-6 of the TMEM231 gene. The 5' boundary is likely confined to intron 3. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. The exact genomic location of this variant is unknown. Gross duplications have not been reported in the literature in individuals with a TMEM231-related disease. In summary, this variant has uncertain impact on TMEM231 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000530783 | SCV000654833 | uncertain significance | Arrhythmogenic right ventricular dysplasia, familial, 13 | 2017-04-07 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exon 7 of the CTNNA3 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals with a CTNNA3-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on CTNNA3 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV000558514 | SCV000658808 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-01-19 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 6-9 of the SMAD3 gene. The 5' boundary is likely confined to intron 5. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with SMAD3-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Rare Disease Group, |
RCV000677251 | SCV000681429 | pathogenic | Optic nerve hypoplasia | criteria provided, single submitter | research | SOX5 previously described in Lamb-Schaffer syndrome that sometimes involves optic nerve hypoplasia. This individual also has intellectual disability and heart defects, also reported in Lamb-Schaffer syndrome. Similar deletions of SOX5 causing the same phenotype have been reported, PMID 22290657. | |
| Broad Institute Rare Disease Group, |
RCV000585924 | SCV000693907 | pathogenic | Glycogen storage disease, type II | 2017-06-25 | criteria provided, single submitter | research | PVS1: Identified truncating variant in compound heterozygote with common promoter pathogenic variant. Previously reported in 2 patients in the literature with adult onset GSDII. PM2: Absent from gnomAD (well covered) and PM3: 3 compound heterozygotes with GSDII, including 2 in literature (PMID: 17616415). |
| Eurofins NTD LLC |
RCV000594755 | SCV000703106 | uncertain significance | not provided | 2017-02-27 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000592422 | SCV000703422 | uncertain significance | not provided | 2017-01-09 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000593500 | SCV000704742 | uncertain significance | not provided | 2017-01-06 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000597577 | SCV000706542 | uncertain significance | not provided | 2017-02-27 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000597921 | SCV000707424 | uncertain significance | not provided | 2017-03-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000603650 | SCV000719684 | likely benign | not specified | 2017-05-26 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Center for Human Genetics and Laboratory Diagnostics, |
RCV000624863 | SCV000740317 | pathogenic | Spherocytosis type 2 | 2018-03-29 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000627115 | SCV000747919 | likely pathogenic | Autistic behavior; Severe global developmental delay | 2012-12-17 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000627116 | SCV000747920 | likely pathogenic | Autistic behavior; Severe global developmental delay | 2017-04-30 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000627117 | SCV000747921 | likely pathogenic | Autistic behavior; Moderate global developmental delay | 2017-05-27 | criteria provided, single submitter | clinical testing | |
| Department of Psychiatry, |
RCV000754118 | SCV000777921 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754119 | SCV000777922 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754124 | SCV000777927 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754129 | SCV000777932 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754131 | SCV000777934 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754132 | SCV000777935 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754147 | SCV000777950 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754155 | SCV000777958 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754156 | SCV000777959 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754157 | SCV000777960 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754158 | SCV000777961 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754160 | SCV000777963 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754162 | SCV000777965 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754164 | SCV000777967 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754166 | SCV000777969 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754167 | SCV000777970 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754168 | SCV000777971 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754171 | SCV000777974 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754172 | SCV000777975 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754173 | SCV000777976 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754174 | SCV000777977 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754175 | SCV000777978 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754177 | SCV000777980 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754179 | SCV000777982 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754180 | SCV000777983 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754182 | SCV000777985 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754184 | SCV000777987 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754185 | SCV000777988 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754186 | SCV000777989 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754188 | SCV000777991 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754189 | SCV000777992 | pathogenic | Autistic disorder; Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754201 | SCV000778004 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754205 | SCV000778008 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754211 | SCV000778014 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754212 | SCV000778015 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754229 | SCV000778032 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754248 | SCV000778051 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754249 | SCV000778052 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754250 | SCV000778053 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754256 | SCV000778059 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754258 | SCV000778061 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754259 | SCV000778062 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754267 | SCV000778070 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754277 | SCV000778080 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754283 | SCV000778086 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754289 | SCV000778092 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754292 | SCV000778095 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754324 | SCV000778127 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754329 | SCV000778132 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754330 | SCV000778133 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754331 | SCV000778134 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754332 | SCV000778135 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754333 | SCV000778136 | pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754334 | SCV000778137 | pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754346 | SCV000778149 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754347 | SCV000778150 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754348 | SCV000778151 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754349 | SCV000778152 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754350 | SCV000778153 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754351 | SCV000778154 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754352 | SCV000778155 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754353 | SCV000778156 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754362 | SCV000778165 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754363 | SCV000778166 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754364 | SCV000778167 | likely pathogenic | Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754365 | SCV000778168 | pathogenic | Autistic disorder; Schizophrenia | 2018-03-20 | criteria provided, single submitter | research | |
| Department of Psychiatry, |
RCV000754378 | SCV000778181 | likely pathogenic | Autistic disorder | 2018-03-20 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754403 | SCV000787664 | uncertain significance | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754413 | SCV000787674 | likely benign | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754448 | SCV000787709 | likely benign | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754469 | SCV000787730 | uncertain significance | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754473 | SCV000787734 | likely benign | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754474 | SCV000787735 | uncertain significance | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000754479 | SCV000787740 | uncertain significance | Primary amenorrhea | 2018-06-01 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000754946 | SCV000788371 | pathogenic | Jeune thoracic dystrophy | 2018-05-01 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000754969 | SCV000788396 | pathogenic | 1q24q25 microdeletion syndrome | 2018-05-01 | criteria provided, single submitter | research | |
| Counsyl | RCV000668947 | SCV000793630 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2017-08-25 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000669077 | SCV000793779 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2017-08-30 | criteria provided, single submitter | clinical testing | |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677147 | SCV000803307 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 8 year old female with intellectual disability, hyperkinesis, seizure disorder, and feeding disorder. She has a history of congenital hip dysplasia, chronic constipation, atrial septal defect, strabismus, and Raynaud's phenomenon. Brain MRI showed mild diffuse loss of the deep white matter in both cerebral hemispheres. This patient also has a pathogenic 43 Mb duplication at 4q. These copy number variants are a result of a derivative chromosome 4. The patient's sister, who is similarly affected, has the same derivative chromosome 4. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677148 | SCV000803308 | pathogenic | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This duplication was identified in an 8 year old female with intellectual disability, hyperkinesis, seizure disorder, and feeding disorder. She has a history of congenital hip dysplasia, chronic constipation, atrial septal defect, strabismus, and Raynaud's phenomenon. Brain MRI showed mild diffuse loss of the deep white matter in both cerebral hemispheres. This patient also has a 770 kilobase deletion at 4pter, which is of uncertain significance. These copy number variants are a result of a derivative chromosome 4. The patient's sister, who is similarly affected, has the same derivative chromosome 4. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677149 | SCV000803309 | pathogenic | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 20 year old female with mild intellectual disability, superimposed expressive language disorder, and ADHD symptoms. X-inactivation analysis showed 84:16 ratio, consistent with moderate skewing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677150 | SCV000803310 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 8 year old female with developmental delays, severe superimposed expressive language disorder, uncertain overall intellectual abilities, ventricular septal defect, short stature, and hypertonia. Jaundice and sacral dimple were noted at birth. Notable facial features include: microcephaly, midface hypoplasia, triangular facies, fine hair, high forehead with broad and prominent brow, protruding low-set ears, epicanthus, deep-set eyes, sparse eyebrows, broad nasal root with low bridge, anteverted nares, small nasal tip, thin lips, small mouth, and small chin. She has proximally placed thumbs with small, abnormal nails. Renal ultrasound was normal. Additionally, a de novo, 23.7 Mb duplication on 9p was identified in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677151 | SCV000803311 | pathogenic | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This duplication was identified in an 8 year old female with developmental delays, severe superimposed expressive language disorder, uncertain overall intellectual abilities, ventricular septal defect, short stature, and hypertonia. Jaundice and sacral dimple were noted at birth. Notable facial features include: microcephaly, midface hypoplasia, triangular facies, fine hair, high forehead with broad and prominent brow, protruding low-set ears, epicanthus, deep-set eyes, sparse eyebrows, broad nasal root with low bridge, anteverted nares, small nasal tip, thin lips, small mouth, and small chin. She has proximally placed thumbs with small, abnormal nails. Renal ultrasound was normal. Additionally, a de novo, 212 kilobase deletion on 9p was identified in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677152 | SCV000803312 | uncertain significance | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 14 year old male with intellectual disability, phonological disorder, ADHD, disruptive behavior, sleep disturbance, and constipation. Renal ultrasound revealed mild left-sided hydronephrosis, but kidneys were otherwise normal. The deletion was not found in his mother but the father was not available for testing. There is a paternal family history of behavior and developmental problems. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677153 | SCV000803313 | pathogenic | Brain malformations and urinary tract defects | 2018-03-01 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 18 year old female with autism spectrum disorder, learning disorder, macrocephaly, and ADHD. Brain MRI at age 2 months showed thinned and high riding corpus callosum. The same deletion was identified in her younger twin sisters, who are more severely impaired, as well as her mother, who has some learning disability but who lives independently. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677154 | SCV000803314 | uncertain significance | Mental retardation, autosomal dominant 26 | 2018-04-03 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 12 year old female autism spectrum disorder, moderate intellectual disability, anxiety, history of seizures, short stature (less than 1st percentile), and low weight (1st percentile). The deletion was maternally inherited, and the mother has no history of neurodevelopmental disorders. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677155 | SCV000803315 | uncertain significance | not provided | 2017-03-27 | criteria provided, single submitter | provider interpretation | This duplication was identified in an 11 year old male with mild to moderate intellectual disability, hyperkinesis, atypical stereotypic movement disorder, disruptive behavior, borderline microcephaly (51.40 cm), short stature (2%ile), and dysmorphic features. The duplication was paternally inherited, and the patient's father is unaffected. Of note, this patient also carries a maternally-inherited VUS in EFNB1 and VUS of unknown inheritance in TLK2. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677156 | SCV000803316 | pathogenic | Generalized juvenile polyposis/juvenile polyposis coli | 2017-05-01 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 8 year old male with autism spectrum disorder and intellectual disability. The patient has not yet had a colonoscopy or endoscopy but is scheduled to begin that surveillance at age 15. His cardiac evaluation was normal. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677157 | SCV000803317 | likely pathogenic | not provided | 2017-05-01 | criteria provided, single submitter | provider interpretation | This duplication was identified in an 8 year old male with autism spectrum disorder and intellectual disability. Given the size of the duplication, the variant has been classified as likely pathogenic. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677158 | SCV000803318 | uncertain significance | not provided | 2018-04-16 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 12 year old female with a history of failure to thrive, infantile seizures, dysmorphic features, precocious puberty, and mild to moderate intellectual disability. Of note, Smith-Lemli-Opitz testing was negative. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677159 | SCV000803319 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 123.5 kilobase deletion was detected in a patient with a history of choanal atresia, TE fistula, supraventricular tachycardia, renal reflux, craniosynostosis, congenital hydrocephalus, global developmental delay, bicuspid aortic valve, undesceneded testes, micropenis, and dysmorphic facial features. This deletion includes two OMIM genes CYP2E1 and SYCE1. This deletion was found to be maternally inherited. The patient's mother does not have a reported history of congenital anomalies or neurodevelopmental concerns. An additional variant identified in the patient was identified and felt to be consistent with CHARGE syndrome. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677160 | SCV000803320 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This approximately 747 kilobase duplication was identified in a male with autism spectrum disorder. This region includes 5 OMIM genes, of which VSP37A and FGF20 have been associated with clinical conditions. Both are associated with autosomal recessive conditions - spastic paraplegia 53 and renal hypoplasia/aplasia 2 respectively. Parental testing has not been completed to date. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677161 | SCV000803321 | uncertain significance | not provided | 2018-04-04 | criteria provided, single submitter | provider interpretation | This 2.6 Mb duplication was identified in a patient with a history of mild intellectual disability, superimposed severe expressive language disorder, congenital heart defect, seizure disorder, and rectal prolapse. The duplication includes approximately 25 known genes. Larger duplications have been reported in individuals with postnatal growth retardation, microcephaly, and characteristic facies (Grossman et al. 2009). This duplication was found to be paternally inherited. The patient's father has a history of speech delay and obesity. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677162 | SCV000803322 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This approximately 395 kilobase duplication was identified in a male with a history of microcephaly, congenital lymphedema of the feet, superimposed expressive language disorder, popliteal cysts and intellectual disability. The duplication includes 7 OMIM genes. Two of these genes are associated with known conditions - TUBB2A and TUBB2B. Heterozygous missense variants in TUBB2B are associated with microcephaly, brain abnormalities, developmental delays, intellectual disability, and seizures. Heterozygous missense variants in TUBB2A have been associated with hypotonia, brain abnormlities, seizures, and intellectual disability. The effect of a duplication of these genes is unclear. This duplication was found to be paternally inherited. The patient's father has a reported history of a learning disability and speech delay. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677163 | SCV000803323 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This approximately 3.3 Mb deletion was detected in an individual with a history of intellectual disability, dyspraxia, hypotonia, epicanthal folds, long facies with bitemporal narrowing, scoliosis, and increased joint laxity. A smaller, nested deletion was described in a patient with developmental delay, muscle hypotonia, dysmorphic features, and skeletal abnormalities (Shimojima et al. 2009). Several similar deletions have also been submitted to ClinVar (SCV000178752; SCV000175474; SCV000502982; SCV000502982). Parental testing has not been completed to date. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677164 | SCV000803324 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This 127.2 kilobase deletion was identified in a 10 year old with a history of autism spectrum disorder, mild impairments of visual-motor/problem-solving skills, and hyperkinesis. Parental testing has not been completed to date. A 1q21.1 duplication (including TAR region) was also identified in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677165 | SCV000803325 | uncertain significance | not provided | 2017-12-01 | criteria provided, single submitter | provider interpretation | This 582 kilobase duplication was identified in an individual with a history of developmental delay with borderline intellectual ability, developmental language impairment, umbilical hernia, and unilateral inguinal hernia. It includes 8 genes: CRLD2, CSF2RA, IL3RA, SLC25A6, ASMTL-AS1, ASMTL, P2RY8, AKAP17A, ASMT. The majority of these genes are not associated with known conditions. The CSF2RA gene is associated with hereditary pulmonary alveolar proteinosis, caused by loss of function of CSF2RA due to gene deletion or protein truncation. The ASMT gene has been implicated as potentially associated with autism spectrum disorders. Several association studies have published a possible increased risk for autism; however, additional studies failed to duplicate this association. Additionally, one publication (Cai et al. 2008) found an interstitial duplication of ASMT at a higher frequency in individuals with autism spectrum disorders compared to controls. This duplication included at least exons 2-8 of ASMT. The significance of entire gene duplications is unclear. Parental testing has not been completed to date. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677166 | SCV000803326 | likely pathogenic | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 720.71 kilobase deletion was identified in a male with a history of autism spectrum disorder, developmental delay, and short stature. The deletion includes the 5' end of the NRXN1 gene and deletes exons 1-5 of the alpha isoform. Variants in the NRXN1 gene, including intragenic copy number variants, have been associated with a variable neurodevelopmental diagnoses including autism spectrum disorders, intellectual disability, epilepsy, and schizophrenia. The features are variable from individual to individual. 2p16.3 deletions and variants in the NRXN1 gene have also been reported in healthy controls and unaffected parents of individuals with neuropsychiatric disorders indicating reduced penetrance or variable expressivity (Schaaf et al. 2012; Bena et al. 2013). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677167 | SCV000803327 | likely pathogenic | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 714.9 kilobase deletion was identified in a male with a history of developmental language disorder, patent foramen ovale, microcephaly, apraxia of speech, and scoliosis. This deletion includes the distal portion of the common 22q11.21 region, but does not include the TBX1 gene and is proximal to BCR. Similar deletions have been reported in individuals with a number of features including growth restriction, developmental delay, intellectual disability, language delay, and dysmorphic features (Burnside 2015; Rauch et al. 2005). The patient's mother reportedly has a history of kyphosis, spinal tumor, and had a normal microarray. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677168 | SCV000803328 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This 1.93 Mb deletion was identified in a 9 year old female with microcephaly, mild intellectual disability, and ADHD. This deletion includes four genes, two of which are associated with known conditions. Single nucleotide variants in CHMP2B have been associated with familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis 17. Frontotemporal dementia due to variants in this gene are thought to result from a build-up of the abnormal protein. The impact of a whole gene deletion is unclear, however. Homozygous or compound heterozygous variants in POU1F1 have been associated with autosomal recessive combined pituitary hormone deficiency. Maternal inheritance of the variant was ruled out, but paternal testing has not been completed. Subsequent whole exome sequencing identified two VUSs in a gene associated with an autosomal recessive condition. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677169 | SCV000803329 | uncertain significance | not provided | 2018-03-28 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 10 year old male with mild hypotonia, autism spectrum disorder, learning disorder, OCD, ADHD, macrocephaly, borderline to mildly impaired verbal abilities with a large verbal/performance split, and was found to be paternally inherited. Proband's father has a history of depression and ADHD, along with a family history of autism. This deletion is within the RBFOX1 (also known as A2BP1) gene, which has not been clearly associated with human diseases. RBFOX1 has been implicated in a range of neurodevelopmental diseases including forms of epilepsy and autism spectrum disorders. It is not clear whether this deletion is related to the patient's neurodevelopmental history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677170 | SCV000803330 | uncertain significance | not provided | 2018-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 13 year old male with borderline intellectual functioning, superimposed expressive communication impairment/verbal apraxia, sleep disturbance, mood lability, irritability, and aggression. Parental testing for this duplication was not completed. Proband is a known carrier of a pathogenic 16p11.2 deletion, to which his symptoms are attributed. Within this duplication three OMIM genes are included; NF2, NEFH, and a portion of EWSR1. The clinical significance of a duplication of these genes is not currently known. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677171 | SCV000803331 | pathogenic | Breast-ovarian cancer, familial 2 | 2018-04-12 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 12 year old male with intellectual disability, autism spectrum disorder, anxiety, and obesity. Parental testing was not completed. This deletion includes three genes, including a portion of BRCA2. The patient's father has a strong family history of breast cancer in individuals under the age of 40 and so the deletion is likely paternally inherited. The father has a history of eye problems (ptosis, pain, diplopia), hypertension, and high cholesterol. Patient has a sister with autism who has not been tested for this deletion. The clinical significance of this deletion for the patient's current symptoms remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677172 | SCV000803332 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 12 year old male with ADHD, oppositional defiant disorder, and a history of language disorder, and was found to be paternally inherited. The patient's father was born with bilateral polydactyly and a congenital heart anomaly. This duplication includes 4 genes, none of which are currently associated with a known clinical syndrome. DECIPHER reports one individual with a small duplication within this region in an individual with hypotonia, intellectual disability/developmental delay, microcephaly, proportionate short stature, and strabismus. The clinical significance of three copies of these genes remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677173 | SCV000803333 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b; Variegate porphyria; Familial hemiplegic migraine type 2; Paragangliomas 3 | 2018-04-13 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 21 year old female with developmental delays and intellectual disability. Parental testing was not completed. This deletion contains approximately 50 genes including MPZ, PPOX, ATP1A2, and SDHC. She is at risk for developing Charcot-Marie-Tooth syndrome (type 1B, 2I, 2J, and dominant intermediate D), porphyria variegata, Hereditary Paraganglioma and Pheochromocytoma syndrome, and has an increased risk for migraines based on this deletion. Notably, she currently has no muscular symptoms consistent with CMT, nor any skin findings consistent with porphyria. Similar overlapping deletions have been seen in individuals with symptoms included but not limited to: intellectual disability, proportionate short statue, dysmorphic features, bilateral cleft lip/palate, hemiatrophy, hypodysplasia of corpus callosum, IUGR, and complex heart defects. This individual also has 16p11.2 deletion syndrome, identified through chromosomal microarray, which is also likely contributing to her developmental phenotype. |
| Rare Disease Group, |
RCV000754985 | SCV000803395 | uncertain significance | Intestinal malrotation | 2018-06-11 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000754990 | SCV000803400 | pathogenic | Intestinal malrotation | 2018-06-11 | criteria provided, single submitter | research | |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677908 | SCV000804063 | likely pathogenic | Cystinuria | 2016-06-16 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 6 year old female with developmental delays, microcephaly, craniosynostosis, hypertrophic cardiomyopathy, and history of acute lymphoid leukemia in remission. This deletion was inherited from a mother with a history of a kidney stone and the maternal grandfather is reported to have multiple kidney stones. Follow up testing for the proband showed elevated urine amino acids. This result indicates carrier status for cystinuria, at minimum. Additionally, 3 variants of uncertain significance were identified by exome sequencing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677909 | SCV000804064 | uncertain significance | not provided | 2018-03-19 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old male with global developmental delay. Brain MRI at age 26 months showed a slightly delayed myelination pattern. Parental testing was not completed. There is a family history of learning and psychiatric illness on both the maternal and paternal side, and a paternal family history of seizures. No facial dysmorphisms were noted. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677910 | SCV000804065 | pathogenic | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 5 year old male with global developmental delays, velopharyngeal insufficiency, VSD, PFO, recurrent otitis media, mild astigmatism, bilateral single transverse palmar creases, narrow left palpebral fissure, full lips, bowed upper lip, and 5th finger clinodactyly. Brain MRI showed mega cisterna magna but was otherwise unremarkable. Parental testing was not completed. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677911 | SCV000804066 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old male with global developmental delays, velopharyngeal insufficiency, VSD, PFO, recurrent otitis media, mild astigmatism, bilateral single transverse palmar creases, narrow left palpebral fissure, full lips, bowed upper lip, and 5th finger clinodactyly. Brain MRI showed mega cisterna magna but was otherwise unremarkable. Parental testing was not completed. Additionally, a 2.478 Mb pathogenic chromosomal deletion was identified in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677912 | SCV000804067 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 6 year old female with slightly upslanted palpebral fissures and autism spectrum disorder. She was born at term with significant issues in the neonatal period including meconium aspiration with respiratory distress, hypotension, metabolic acidosis, HIE, persistent fetal circulation, adrenal hypofunction, thrombocytopenia, and anemia. Parental testing was not available. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677913 | SCV000804068 | uncertain significance | not provided | 2018-02-05 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 5 year old female with autism spectrum disorder, global developmental delays, hyperkinesis, ADHD, feeding problems, sleep problems, and wide spaced teeth. The deletion was inherited from a father with ADHD and bipolar disorder. Follow up ophthalmological exam was normal and the father has normal vision. This history supports the putative PAX6 downstream regulatory region proposed by Balay et al, 2015 (PMID:26419218), which is not included in this patient's deletion region. It is not clear whether this deletion is related to the patient neurodevelopmental history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677914 | SCV000804069 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 20 year old male with autism spectrum disorder, sleep disturbance, mood disorder, anxiety, macrocephaly, a vocal tic, and obesity. He has astigmatism, eczema, and a history of frequent epistaxis. There is no paternal history of neurodevelopmental disorders. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677915 | SCV000804070 | likely benign | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 7 year old male with a history of global developmental delay (intellectual ability are uncertain) and superimposed expressive language delay. He has echolalia and will point in a protoimperative and protodeclarative manner. He is making progress with expressing emotions and will follow a familiar two-step command. He was found to have a pathogenic 8.2 Mb duplication of 18p11.32p11.22 by microarray. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677916 | SCV000804071 | pathogenic | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 7 year old male with a history of global developmental delay (intellectual ability are uncertain) and superimposed expressive language delay. He has echolalia and will point in a protoimperative and protodeclarative manner. He is making progress with expressing emotions and will follow a familiar two-step command. The duplication was also found in the patient's mother, who has a history of ADHD and learning disability. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677917 | SCV000804072 | uncertain significance | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 9 year old male with mild intellectual disability, expressive language delay, inattentiveness, and hyperkinesis. The duplication was inherited from a mother with no significant neurodevelopmental problems. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677918 | SCV000804073 | pathogenic | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 5 year old male with global developmental delays, mild neuromotor abnormalities, stereotypy, macrocephaly, and large stature. He is monitored for seizures due to spells. He has had normal cardiac echo and ECG, normal cranial ultrasound, normal renal ultrasound (except for a urachal cyst). The deletion was inherited from a father with a history of speech delay, learning disability, bipolar disorder, depression, anxiety, substance abuse, heart murmur, and congenital pancreatic divisum. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677919 | SCV000804074 | likely benign | not provided | 2018-02-26 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 10 year old male with autism spectrum disorder, large stature, anxiety, compulsive behavior, and uncertain intellectual abilities. The duplication was inherited from the patient's mother, who does not report learning or developmental problems. There is a maternal family history of psychiatric illness. Additionally, a de novo copy number gain at 19p13.2 was identified by CMA, and 2 variants of uncertain significance were identified by exome sequencing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677920 | SCV000804075 | uncertain significance | not provided | 2018-02-26 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 10 year old male with autism spectrum disorder, large stature, anxiety, compulsive behavior, and uncertain intellectual abilities and was found to be de novo. Additionally, a maternally-inherited copy number gain at 6p22.3 was identified by CMA, and 2 variants of uncertain significance were identified by exome sequencing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677921 | SCV000804076 | likely pathogenic | not provided | 2018-02-05 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 9 year old male with agenesis of the corpus callosum, macrocephaly secondary to enlarged third ventricle, ADHD, and a family history of psychiatric illness. His biological mother has agenesis of the corpus callosum, Tourette's syndrome, and depression. A maternal uncle has schizophrenia, agenesis of the corpus callosum, seizure disorder, and bipolar disorder. The maternal grandfather had schizophrenia and agenesis of the corpus callosum, and a maternal great uncle also had agenesis of the corpus callosum. Parental or other family member testing was not possible. This duplication includes the SHH gene and additional duplications in the literature suggest it is causative for this patient's clinical features (Heide, 2017; Wong, 2015). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677922 | SCV000804077 | likely pathogenic | Mental retardation, autosomal dominant 18 | 2018-02-05 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 4 year old female with global developmental delays, macrocephaly, telecanthus, and a wide based gait. It was found to be de novo and likely impacts expression of the GATAD2B gene due to loss of regulatory region. Clinical correlation with previously reported patients with GATAD2B-related disorder was thought to be very good. In addition, this patient has a paternally-inherited, likely benign duplication at 4q22.3. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677923 | SCV000804078 | likely benign | not provided | 2018-02-05 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old female with global developmental delays, macrocephaly, telecanthus, and a wide based gait. It was inherited from a clinically unaffected father. In addition, this patient carries a de novo, likely pathogenic deletion at 1q21.3. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677924 | SCV000804079 | uncertain significance | not provided | 2018-02-26 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 17 year old male with learning disorder and high functioning autism spectrum disorder. He has a recent diagnosis of sinus tachycardia. This duplication was inherited from the patient's mother, who has a history of anxiety disorder and obsessive-compulsive disorder. Her identical twin sister has a history of depression and severe obsessive-compulsive disorder. This patient's sister, who has mild autism and a phonological disorder, also carries this duplication. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677925 | SCV000804080 | uncertain significance | not provided | 2018-02-05 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with mild global developmental delays, receptive/expressive language disorder, hypotonia, microcephaly, and short stature. Brain MRI revealed pachygyria. Ophthalmology and endocrinology evaluations were normal. This patient's mother, who carries this variant, has learning disability. She has not had subsequent brain imaging. In addition, this patient and his mother were found to carry a novel missense variant in the TUBB2B gene. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677926 | SCV000804081 | pathogenic | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old female with global developmental delays, hearing impairment, sleep problems, short stature, esotropia, chronic constipation, anemia, and small PFO. Renal ultrasound was normal. Notable facial features include a long, narrow face, upslanting palpebral fissures, infraorbital creases, bulbous nasal tip, anteverted nares, and mild retrognathia. This patient also has a pathogenic 39 Mb terminal deletion of Xp22.3p11.2. These copy number variants are a result of a de novo rearrangement: 46,X,der(X)t(X;15)(p11.4;q11.2). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677927 | SCV000804082 | pathogenic | not provided | 2018-04-05 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 4 year old female with global developmental delays, hearing impairment, sleep problems, short stature, esotropia, chronic constipation, anemia, and small PFO. Renal ultrasound was normal. Notable facial features include a long, narrow face, upslanting palpebral fissures, infraorbital creases, bulbous nasal tip, anteverted nares, and mild retrognathia. This patient also has a pathogenic 71 Mb terminal duplication of 15q13.2q26.3. These copy number variants are a result of a de novo rearrangement: 46,X,der(X)t(X;15)(p11.4;q11.2). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677928 | SCV000804083 | likely benign | not provided | 2018-02-26 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 6 year old male with a language disorder, delayed adaptive skills, hypotonia, and short stature. It was inherited from his clinically unaffected mother, who also has no vision abnormalities. Copy number gains of the GUCA1A and GUCA1B genes have been observed in the ExAC database. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677929 | SCV000804084 | uncertain significance | not provided | 2017-06-12 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 3 year old female with develomental delays. She is non-dysmorphic and has a strong maternal family history of psychiatric disorders, seizures, and intellectual disability. Paternal history is unknown. Parental samples were not available for testing. Additionally, a variant of uncertain significance was identified by whole exome sequencing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677930 | SCV000804085 | uncertain significance | not provided | 2017-08-03 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 3 year old male with global developmental delay, expressive language disorder, mild hypotonia, short stature, dolichocephaly, laterally arched eyebrows, epicanthal folds, bulbous nasal tip, bowed upper lip, small toes, sleep disorder, and a history of prematurity. It was inherited from an unaffected mother. It is also a fairly gene-poor region. Additionally, whole exome sequencing identified a de novo, likely pathogenic sequence variant which most likely explains this patient's clinical history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677931 | SCV000804086 | pathogenic | Becker muscular dystrophy | 2017-05-16 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 10 year old male with mild intellectual disability, ADHD, oppositional-defiant disorder, and a history of gastroschisis. Muscle tone and strength appeared normal on exam and there were no gait abnormalities. CK levels, taken after identification of DMD deletion, were significantly elevated (2287). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677932 | SCV000804087 | pathogenic | not provided | 2017-10-31 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 4 year old female with autism spectrum disorder, global developmental delay, and mild hypotonia. She walked at age 2 but currently there are no motor concerns. She has significant language delay with no spoken words, does not point to request, and appears to understand only a few words (receptive age equivalent 10 months). She is slightly short (5th percentile). She has a long philtrum but is otherwise non-dysmorphic. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677933 | SCV000804088 | uncertain significance | not provided | 2018-03-29 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 6 year old male with autism spectrum disorder, disruptive behavior, hyperactivity, persistent insomnia, coordination disorder, and cyclic vomiting syndrome. Only a maternal sample was available for testing, and the patient's mother does not carry the deletion. Of note, this patient also carries a variant of uncertain significance in the ADCY5 gene. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677934 | SCV000804089 | pathogenic | Schizophrenia 17 | 2017-07-29 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 5 year old male with mild intellectual disability, ADHD, mild phonological disorder, and disruptive behavior disorder. Parental testing was not completed. There is an extensive family history of substance abuse, psychiatric diagnoses, and learning disabilities. Two additional copy number variants were also identified in this patient, one likely pathogenic and one of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677935 | SCV000804090 | likely pathogenic | Spinocerebellar ataxia type 27 | 2017-07-29 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 5 year old male with mild intellectual disability, ADHD, mild phonological disorder, and disruptive behavior disorder. Parental testing was not completed. There is no family history of movement disorders. The patient does not currently show any signs of tremor, dyskinesia, or ataxia. He is described by his family as more uncoordinated than his peers. There are reports of individuals with FGF14-related cerebellar ataxia not presenting with motor abnormalities until later in childhood, so the patient will continue to be monitored. Two additional copy number variants were also identified in this patient, one that is pathogenic and one of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677936 | SCV000804091 | uncertain significance | not provided | 2017-07-29 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old male with mild intellectual disability, ADHD, mild phonological disorder, and disruptive behavior disorder. Parental testing was not completed. The region is not known to vary in copy number in the normal population, but none of the genes in the region are currently associated with known clinical disorders. Two additional copy number variants were also identified in this patient, one that is pathogenic and one that is likely pathogenic. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677937 | SCV000804092 | uncertain significance | not provided | 2014-11-12 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 7 year old male with global developmental delays, phonological disorder, ADHD, and disruptive behavior. The deletion was inherited from his mother, who has a history of learning disabilities and ADHD. The deletion is also present in the patient's brother, who has a history of abnormal number of umbilical cord vessel, cardiac defect, and bilateral clubfoot deformity. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677938 | SCV000804093 | pathogenic | Deafness, autosomal recessive 16 | 2018-03-29 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 3 year old female with bilateral sensorineural hearing loss, mixed receptive-expressive language disorder, mild visual-motor delay, mild hypotonia, and gross motor delay. While parental studies have not been done, both of the patient's sisters are homozygous for the same 15q15.3 deletion and both have hearing impairments, suggesting that the parents are each a carrier of the deletion. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677939 | SCV000804094 | pathogenic | Becker muscular dystrophy; Duchenne muscular dystrophy; Dilated cardiomyopathy 3B | 2017-02-06 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 8 year old female with autism spectrum disorder and intellectual disability. The deletion was maternally inherited, and the mother has a history of language delays in childhood, learning impairment, depression, anxiety, and bipolar disorder. She reported a family history of Duchenne muscular dystrophy. One of the patient's maternal uncles died at age 21, and another maternal uncle died at age 12 following anesthesia complications during surgery; they were both reported to have DMD. Neither the patient nor her mother have been evaluated by cardiology to assess for cardiomyopathy. Additionally, neither the patient nor her mother have a history of muscle weakness or gait abnormalities. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677940 | SCV000804095 | likely pathogenic | Nemaline myopathy 6 | 2018-04-12 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 12 year old male with autism spectrum disorder, history of right talipes equinovarus, and leg length discrepancy. Parental studies (targeted microarray and FISH analysis) revealed that this deletion arose de novo. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677941 | SCV000804096 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 12 year old male with intellectual disability and history of multiple non-traumatic fractures. While this duplication was de novo, the patient's father has a history of multiple fractures. Of note, this patient has had negative sequencing and deletion/duplication analaysis of the COL1A1 and COL1A2 genes. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677942 | SCV000804097 | pathogenic | not provided | 2018-04-15 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old female with global developmental delays, short stature, basiocciput hyperplasia and associated basilar invagination, and an arachnoid cyst. Parental studies were performed, and the duplication was found to be de novo. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677943 | SCV000804098 | pathogenic | Axenfeld-Rieger syndrome type 3 | 2018-04-16 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 9 year old female with intellectual disability, microcephaly, craniosynostosis, left hemifacial microsomia, feeding disorder, congenital heart defects, congenital hypothyroidism, renal hypodysplasia/stage 3 chronic kidney disease, ptosis, alternating esotropia, recurrent otitis media, small teeth, and history of prematurity (born at 34 weeks). The deletion was inherited from the patient's father who carries a balanced chromosome translocation (46,XX,der(21),t(6;21)(p21.3q22.3)pat). Because of the patient's intolerance to opthalmological exams, it is not known whether or not she shows signs of glaucoma. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677944 | SCV000804099 | pathogenic | not provided | 2018-04-16 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 9 year old female with intellectual disability, microcephaly, craniosynostosis, left hemifacial microsomia, feeding disorder, congenital heart defects, congenital hypothyroidism, renal hypodysplasia/stage 3 chronic kidney disease, ptosis, alternating esotropia, recurrent otitis media, small teeth, and history of prematurity (born at 34 weeks). The duplication was inherited from the patient's father who carries a balanced chromosome translocation (46,XX,der(21),t(6;21)(p21.3q22.3)pat). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677945 | SCV000804100 | uncertain significance | not provided | 2017-10-09 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with global developmental delays. The duplication was paternally inherited, and the patient's father has a history of learning disabilities and bipolar disorder. The region is not known to vary in copy number in the normal population. The two genes in this region that are associated with human disease (SUMF1, ITPR1) are not known to cause disease when duplicated. Of note, this patient also carries the recurrent 22q11.2 duplication. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677946 | SCV000804101 | uncertain significance | not provided | 2018-04-15 | criteria provided, single submitter | provider interpretation | This duplication was identified in an 18 year old male with mild intellectual disability, ADHD, disruptive behavior, and microcephaly (5th percentile). The patient's mother does not carry the duplication, and a paternal sample is unavailable. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677947 | SCV000804102 | uncertain significance | not provided | 2017-01-10 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 6 year old male with intellectual disability and motor stereotypies. The deletion was found to be maternailly-inherited; the patient's mother is unaffected. The deletion encompasses the non-coding exon 1 of RBFOX1. Haploinsuffiency of RBFOX1 has been implicated in several neurodevelopmental phenotypes, and some deletions have been inherited from a phenotypically normal parent. Of note, this patient also carries a paternally-inherited VUS in the SHANK2 gene. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677948 | SCV000804103 | uncertain significance | Dilated cardiomyopathy 1W; Familial hypertrophic cardiomyopathy 15 | 2015-10-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old female with autism spectrum disorder, global developmental delays, and a feeding disorder. Parental testing has not been performed. Family history is significant for a cerebrovascular accident in the patient's mother at age 36, but there is no known history of cardiomyopathy. Of note, this patient's whole exome sequencing has thus far been negative. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677949 | SCV000804104 | uncertain significance | Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis | 2017-03-23 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 7 year old male with autism spectrum disorder. The duplication was maternally inherited, and his mother does not have a history of hearing impairment or learning disabilities. She does have a history of kidney stones; loss of function variants in AMMECR1, which is within this duplicated region, are associated with nephrocalcinosis. The patient does not have a history of any kidney concerns. Of note, the patient's whole exome sequencing has thus far been normal. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677950 | SCV000804105 | uncertain significance | not provided | 2017-06-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with autism spectrum disorder and global developmental delays. The duplication was maternally inherited, and this individual's mother does not have a history of neurodevelopmental disorders. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677951 | SCV000804106 | uncertain significance | Mental retardation, autosomal dominant 26 | 2017-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with autism spectrum disorder, global developmental delays, and agenesis of the corpus callosum. The duplication was maternally-inherited, and the patient's mother has a history of depression and anxiety. The patient also carries a maternally inherited duplication of uncertain significance at 18q21.2. Of note, this patient's whole exome sequencing has thus far been normal. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677952 | SCV000804107 | uncertain significance | Mirror movements 1 | 2017-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with autism spectrum disorder, global developmental delays, and agenesis of the corpus callosum. The duplcation was inherited from his mother, who has a history of anxiety and depression. The patient also carries a duplication of uncertain significance at 7q11.22. Of note, his whole exome sequencing has thus far been negative. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677953 | SCV000804108 | uncertain significance | not provided | 2017-03-26 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 7 year old male with autism spectrum disorder, history of developmental delays with uncertain intellectual abilities, and self-injurious behaviors. The duplication is maternally-inherited; the patient's mother has a history of anxiety and depression. Of note, the patient was found to carry a variant of uncertain significance in KIF4A through whole exome sequencing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677954 | SCV000804109 | uncertain significance | not provided | 2014-01-24 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 15 year old male with autism spectrum disorder, intellecutal disability, disruptive behavior, sleep disturbances, and staring episodes. The deletion was found to be maternally inherited; his mother has a history of depression and phenomic disorder. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677955 | SCV000804110 | uncertain significance | not provided | 2017-05-01 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 16 year old female with autism spectrum disorder and intellectual disbaility. Parental studies were never performed, so inheritance is unknown. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677956 | SCV000804111 | uncertain significance | not provided | 2016-12-08 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 3 year old male with autism spectrum disorder and global developmental delays. The duplication was paternally inherited, and the patient's father has a history of learning disabilities, childhood speech delay, childhood seizures, and anxiety. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677957 | SCV000804112 | uncertain significance | not provided | 2017-06-08 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 16 year old male with intellectual disability and growth failure. Of note, this patient also carries a de novo likely pathogenic variant in the ZNF711 gene, which is felt to explain his intellectual disability. The patient's mother is unaffected. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677958 | SCV000804113 | pathogenic | Hyperparathyroidism 1; Parathyroid carcinoma; Hyperparathyroidism 2 | 2017-04-25 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 13 year old female with borderline intellectual disability, motor coordination disorder, ADHD, skull anomalies, history of neonatal seizure, and amblyopia. The patient's biological parents are unavailable for parental studies. There is no known family history of parathyroid cancer or thyroid disease. Of note, the patient also carries a pathogenic deletion at 16p11.2. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677959 | SCV000804114 | uncertain significance | not provided | 2017-05-01 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 3 year old female with autism spectrum disorder and global developmental delays. The duplication is maternally-inherited, and the mother has no history of neurodevelopmental disorders. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677960 | SCV000804115 | uncertain significance | not provided | 2017-05-17 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old female with global developmental delays and autism spectrum disorder. The duplication was found to be paternally inherited. The patient's father required learning supports in school. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677961 | SCV000804116 | uncertain significance | not provided | 2017-05-19 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 11 year old male with left hemiplegia, mild intellectual disability, seizure disorder, and hypothyroidism. Parental samples are unavailable, so inheritance is unknown. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677962 | SCV000804117 | uncertain significance | Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) | 2017-08-10 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old female with global developmental delays. Parental samples are unavailable, so inheritance is unknown. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677963 | SCV000804118 | uncertain significance | not provided | 2018-01-31 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with autism spectrum disorder and speech delay. The duplication was found to be maternally inherited, and the patient's mother received learning supports in school. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677964 | SCV000804119 | pathogenic | Exudative vitreoretinopathy 1 | 2017-10-18 | criteria provided, single submitter | provider interpretation | This deletion was identified in an 11 year old male with autism spectrum disorder and intellectual disability. The patient does not tolerate thorough opthalmological evaluations, but he is not reported to show any signs of retinopathy at his current age. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677965 | SCV000804120 | uncertain significance | Congenital plasminogen activator inhibitor type 1 deficiency | 2017-10-18 | criteria provided, single submitter | provider interpretation | This duplication was identified in an 11 year old male with autism spectrum disorder and intellectual disability. The duplication was maternally-inherited, and neither the patient nor his mother are reported to have abnormal bleeding after trauma or surgery. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677966 | SCV000804121 | uncertain significance | not provided | 2018-04-11 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 12 year old male with autism spectrum disorder, ADHD, history of global developmental delay (resolved, IQ currently in average range), and history of bilateral clubfoot deformity. The duplication was paternally inherited, and the patient's father has learning difficulties and a history of anxiety and depression. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677967 | SCV000804122 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 6 year old male with autism spectrum disorder, global developmental delay, hypotonia, a heart murmur, feeding problems, GERD, and a history of a unilaterial inguinal hernia, and was found to be maternally inherited. The patient's mother does not have a history of any neurodevelopmental disorders. Notably, neither this patient nor his mother have any hand, foot, or bone defects. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677968 | SCV000804123 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 6 year old male with autism spectrum disorder, global developmental delay, hypotonia, a heart murmur, feeding problems, GERD, and a history of a unilaterial inguinal hernia. The duplication was found to be maternally inherited. The patient's mother does not have a history of any neurodevelopmental disorders. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677969 | SCV000804124 | uncertain significance | Macrocephaly, macrosomia, facial dysmorphism syndrome | 2018-02-23 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with autism spectrum disorder, global developmental delay, and history of prematurity (born at 28 weeks). The duplication was maternally inherited, and the mother has a history of learning disability and depression. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677970 | SCV000804125 | uncertain significance | not provided | 2017-08-21 | criteria provided, single submitter | provider interpretation | This 924 kilobase duplication includes portions of the NKAIN2 and TRDN genes. TRDN is associated with autosomal recessive catecholaminergic polymorphic ventricular tachycardia-5 with or without muscle weakness. NKAIN2 is not currently associated with any known disorders. Disruption of NKAIN2 due to de novo rearrangements have been reported in two patients previously (Yue et al. 2006; Bocciardi et al. 2005). One individual with disruption at exon 4 had a clinical history of a congenital heart defect, macrocephaly, undescended testes, recurrent infections, and developmental delays (Yue et al. 2006). The second individual's translocation disrupted the gene in intron 4 had a history of neurologic abnormalities including including epileptic encephalopathy with spastic tetraparesis and severe psychomotor retardation associated with cerebral atrophy with involvement of the periventricular white matter (Bocciardi et al. 2005). Similar, overlapping duplications have been reported in several individuals in DECIPHER including in an individual with cognitive impairment (Case: 300577) and an individual with short stature (Case:331671). Overlapping variants have also been submitted to dbVar/ClinVar previously (nssv582678; nsv2777188; nsv534388) and reported in developmental delay cohorts as well as in controls (nsv1022195; nsv1018599). A similar duplication has been reported in the literature in an individual with facial dysmorphism, severe developmental delay, complex neurological impairment and spasticity (Sheth et al. 2015). Both unaffected, consanguinous parents carried that duplication, however. Given that similar duplications have been reported in individuals with neurodevelopmental concerns as well as in control populations and unaffected parents, the clinical significance of this variant is unclear. This patient also had a maternally inherited, pathogenic 1q21.1q21.2 duplication identified on chromosomal microarray that provides an explanation for his autism spectrum disoder, speech delay, and other phenotypic features. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677971 | SCV000804126 | uncertain significance | not provided | 2017-10-31 | criteria provided, single submitter | provider interpretation | This 259 kilobase duplication includes a portion of the PARK2 gene. The PARK2 gene is associated with autosomal recessive juvenile parkison disease type 2. Copy number variants (deletions and duplications) including PARK2 have been reported at a higher prevalence in individuals with ADHD compared to controls, suggesting deletions and duplications of PARK2 may be associated with increased susceptibility of ADHD (Jarick et al. 2014). Deletions and duplications including PARK2 have been suggested as a possible genetic suscpetibility of autism spectrum disorder (Glessner et al. 2009; Yin et al. 2016). A duplication also has been identified in an individual with cognitive impairments who is underweight and has short stature (Scheuerle & Wilson 2011). PARK2 partial gene duplications have been reported in DECIPHER in individuals with intellectual disability and behavioral abnormalities (279450; 279451). The copy number variants reported previously contain multiple exons, whereas, this patient's duplication only includes exon 2 of the gene. PARK2 copy number variants have also been identified in control populations (nsv605163; nsv605167; nsv1034495; nsv1021711; nsv1019976). Follow-up quantitative PCR confirmed overexpression of PARK2 in both the patient and his father suggesting this duplication was paternally inherited. The patient's father has a reported history of dyslexia and learning disability in early schooling. Based on the relatively low number of patients reported in the literature and the presence of duplications and deletions in healthy controls/unaffected parents, further evidence is needed to definitively classify this variant. Whole exome sequencing was also completed for this patient and a paternally inherited variant of uncertain significance was identified. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677972 | SCV000804127 | uncertain significance | not provided | 2017-10-07 | criteria provided, single submitter | provider interpretation | This 758 kilobase deletion includes four genes - BEND3, PDSS2, SOBP, and SCML4. PDSS2 is associated with primary coenzyme Q10 deficiency -3 (OMIM 614652) and SOBP is associated with intellectual disability, anterior maxillary protrusion and strabismus (OMIM 613671). Smaller overlapping deletions have been reported in DECIPHER, including in an individual with global developmental delay, macrocephaly, and abnormality of the philtrum who was large for gestational age (Case 262370) and an individual with a de novo deletion with a history of autism spectrum disorder, delayed speech and language, intellectual disability, microcephaly, and ventricular septal defect (Case 254740). The deletion in our patient was found to be maternally inherited. The patient's mother reportedly had difficulty in reading and math but did not require additional learning supports. The patient also underwent clinical whole exome sequencing that was negative. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677973 | SCV000804128 | uncertain significance | not provided | 2017-10-30 | criteria provided, single submitter | provider interpretation | The 211 kilobase duplication on chromosome 22 contains 4 genes (TXN2, FOXRED2, EIF3D, and a portion of CACNG2), none of which are known to be associated with a clinical disorder when duplicated. The TXN2 gene is associated with autosomal recessive oxidative phosphylation deficiency- 29 and CACNG2 has been reported to cause autosomal dominant intellectual disability due to loss of function variants. A smaller overlapping duplication was identified in a developmental delay cohort (nsv1064827). An overlapping duplication has also been reported in a control (nsv1060004). Parental testing for our patient showed that this variant was paternally inherited. The patient's father does not have a history of autism spectrum disorders or developmental differences making this variant less likely to be anexplanation for the patient's neurodevelopmental history. The patient also underwent whole exome sequencing that identified a de novo variant in a gene of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677974 | SCV000804129 | uncertain significance | not provided | 2018-02-02 | criteria provided, single submitter | provider interpretation | This 507 kilobase duplication was detected in an individual with developmental delay, autism spectrum disorder, dermititis, and sleep difficulties. This duplication includes a portion of the TWIST2 and HDAC4 genes. TWIST2 is associated with the autosomal recessive disorder focal facial dermal dysplasis 3, Setleis type. Haploinsufficiency of HDAC4 is associated with brachydactyly-mental retardation syndrome. Duplications of these genes have not been associated with any particular conditions, however. The genetic testing laboratory indicated that they have seen duplications in the area, and several other duplications have been reported in DECIPHER, including a smaller overlapping variant in an individual with an abnormal face shape and intellectual disability (Case: 282651). This area is not known to vary in the general population. Parental testing has not been completed to date to determine if this variant is de novo or inherited. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677975 | SCV000804130 | likely pathogenic | not provided | 2017-11-16 | criteria provided, single submitter | provider interpretation | This approximately 9.1 Mb deletion was detected in a 10 year old male with a history of expressive language disorder, autism spectrum disorder, sleep difficulties, and ADHD. This deletion includes 25 genes, 4 of which have been associated with clinical disorders. Two genes, NEK1 and MSMO1, are associated with autosomal recessive conditions indicating the patient is a carrier for these conditions. Heterozygous missense variants in the TLL1 gene have been associated with atrial septal defects (Stanczak et al. 2009). A single missense variant in PALLD has been reported to increase susceptibility to pancreatic cancer. PALLD has conflicting literature regarding its link to pancreatic cancer risk, however. Some publications indicate a risk while other literature refutes this. Functionally, this variant has been shown to result in overexpression of the gene, and overexpression of the gene is not expected with a gene deletion (Pogue-Geile et al. 2006). Overlapping deletions have been reported in the literature in an individual with Robin sequence, mild developmental delays and ulnar anomalies and another individual with congenital heart defect, growth delay, and minor skeletal anomalies (Keeling et al. 2001; Xu et al. 2012). Overlapping deletions have been identified in several individuals in DECIPHER including an individual with a broad forehead, downslanted palpebral fissures, high anterior hairline, and intellectual disability (Case 257358). An overlapping variant was also submitted to ClinVar/dbVar in an individual with abnormal facial shape and learning disability (nsv532029). A follow-up echocardiogram for the patient was normal. Parental follow-up testing identified that this deletion is secondary to a maternal balanced rearrangement. Maternal family history includes a relative with multiple miscarriages, a pregnancy with congenital anomaly of the brain/skull, and a child with a congenital heart defect suggesting others in the family may also carry the balanced rearrangement. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677976 | SCV000804131 | uncertain significance | not provided | 2018-03-16 | criteria provided, single submitter | provider interpretation | This 305 kilobase duplication was identified in an individual with autism spectrum disorder, delayed milestones, hyperopia, and asthma. This duplication includes portions of the SHOX and PPP2R3B genes. Nonsense variants and deletions of SHOX have been reported in individuals with idiopathic short stature and Leri-Weill dyschondrosteosis (Huber et al. 2001; Niesler et al. 2002; Rappold et al. 2002). Partial or complete duplications of SHOX and/or its enhancer regions have also been reported in patients with these conditions (Thomas et al. 2009; Benito-Sanz et al. 2011). Duplications of SHOX have also been reported in individuals with tall stature. Tropeano et al. 2016 identified an enrichment of SHOX microduplications in individuals with neurodevelopmental disorders including autism sprectrum disorders compared to controls. The patient's father also was found to carry this duplication although testing could not determine if the variant is on his father's X or Y chromosome since its location on the Y chromosome in the patient could be the result of recombination between the X and Y chromosomes in his father. The patient's father is also of typical height but does have a reported history of speech delay and learning disability. The patient was found to also carry a maternally inherited, distal 16p11.2 deletion. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677977 | SCV000804132 | uncertain significance | not provided | 2018-03-19 | criteria provided, single submitter | provider interpretation | This 393 kilobase duplication was identified in an individual with autism spectrum disorder, intellectual disability, ADHD, constipation, hypotonia, and expressive language disorder. This duplication is within cytogenetic band 16p13.3. The duplication includes 15 entire genes and the portion of two additional genes. Four genes are associated with clinical conditions - TSC2, PKD1, ABCA3, and TBC1D24. A portion of TSC2 is included in this duplication. Heterozygous loss of function variants in TSC2 are associated with tuberous sclerosis-2 and heterozygous loss of function variants in PKD1 are associated with adult type 1 polycystic kidney disease. ABCA3 is associated with autsomal recessive pulmonary surfactant metabolism dysfunction, and TBC1D24 is associated with several autosomal recessive conditions including early infantile epileptic encephalopathy, familial infantile myoclonic epilepsy, autosomal recessive deaness, and DOOR syndrome. Slightly larger duplications have been reported in DECIPHER in an individual with a kidney abnormality and mild intellectual disability (Case 263885) and in the general population in a single individual (chr16:2124547-2679656). No smaller overlapping duplications have been reported. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677978 | SCV000804133 | pathogenic | not provided | 2018-03-19 | criteria provided, single submitter | provider interpretation | This 13.9 Mb duplication from cytogenetic band 20p12.2 to 20q11.21 was determined to be present in the form of a supernumerary marker chromosome in an 8 year old male with a history of syndactyly of the toes, speech delay, developmental delay, nystagmus, and spontaneous pneumothorax. In particular, this result likely is indicative of a ring chromosome. This supernumerary chromosome was identifid in 88% of cells. Ring chromosomes of a similar size have been reported in databases in and in the literature (http://ssmc-tl.com/sSMC.html; Daber et al. 2012; Kitsiou-Tzeli et al. 2009; Guediche et al. 2010). Reported phenotypes of individuals with supernumerary marker chromosome are highly variable with unaffected individuals, growth retardation, atrial septal defect, facial dysmorphism, and developmental delay (Daber et al. 2012; Guediche et al. 2010; Kitsiou-Tzeli et al. 2009). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677979 | SCV000804134 | uncertain significance | not provided | 2018-03-19 | criteria provided, single submitter | provider interpretation | This 82 kilobase duplication was identified in a patient with a history of autism spectrum disorder and global developmental delay. The duplication includes only the NDP gene. Loss of function of the NDP is associated with Norrie disease and exudative vitreoretinopathy, features of which include blindness in infancy, progressive hearing loss, developmental delays, intellectual disability, and psychosis. Females may rarely have some clinical manifestations. The impact of duplications of the NDP gene are unclear. This region is not known to vary in the general population. The patient's mother was found to carry this same duplication. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677980 | SCV000804135 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | provider interpretation | This 960 kilobase duplication was identified in a patient with a history of macrocephaly, dysmorphic features, atrial septal defect, agenesis of the corpus callosum, seizures, feeding disorder and global developmental delays. Parental testing confirmed this duplication was maternally inherited. This patient's mother has a reported history of anxiety, depression, and a mild learning disability. The duplication includes a portion of the CTNND2 gene, a gene that has been suggested to play a role in severity of intellectual disability in cri-du-chat syndrome. The impact of a partial duplication of this gene is unclear. Partial duplications have been reported in association with schizophrenia and in an individual with cerebral palsy (Vrijenhock et al. 2008; McMichael et al. 2014). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677981 | SCV000804136 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 1.1 Mb duplication within Xq12 was identified in a patient with a history of autism spectrum disorder and expressive speech delay. The duplication includes the EDA2R and AR genes. Smaller duplications within this region have been identified in individuals with intellectual disability (Madrigal et al. 2007; DECIPHER Case 249562). This duplication was identified in this patient's mother who has a reported history of a learning disability. A 15q11.2 deletion was also identified in this patient and his mother. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677982 | SCV000804137 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 431 kilobase duplication was identified in a female patient with a history of developmental delay, eczema, and a receptive-expressive language disorder. This duplication was inherited from the patient's mother who reportedly has a history of learning difficulties and anxiety. This duplication includes 13 genes. Of those genes, only STK13 has been associated with a clinical condition. Specifically, STK13 is associated with autosomal recessive spermatogenic failure in males. The relevance of a duplication of this, or any of the other included genes, is unknown. Smaller, overlapping duplications in this region have been reported in DECHIPER in an individual with macrocephaly, hydrocephalus, and intellectual disability (Case 288189), an individual with inappropriate behavior and intellectual disability (Case 288524), and an individual with intellectual disability and psychosis (Case 290429). Smaller, overlapping duplications have also been reported in controls (Cooper et al. 2011). |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677983 | SCV000804138 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 804 kilobase deletion was identified in a patient with speech delay , hypotonia, disruptive behaviors, learning disorder and dysmorphic features. The deletion includes seven genes, none of which have been associated with clinical disorders. The deletion was not identified in the patient's mother. His father has not undergone testing to date. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677984 | SCV000804139 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 184 kilobase duplication was identified in a male with global developmental delay, microcephaly, autism spectrum disorder, hearing impairment, idiopathic toe walking, and dysmorphic features. The duplication includes 6 genes, only one of which, NSDHL, has been associated with a clinical condition. The effect of a duplication of this gene, or the others included, is unclear. The patient's mother was found to also carry this duplication. His mother does not have a reported history of neurodevelopmental concerns. The patient also underwent whole exome sequencing and was found to carry two variants of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677985 | SCV000804140 | likely pathogenic | Dilated cardiomyopathy 1G | 2017-12-04 | criteria provided, single submitter | provider interpretation | This deletion was identified in a patient with a history of intellectual disability, autism spectrum disorder, and insomnia. A mitochondrial disorder has previously been suspected. The deletion includes a portion of the TTN and PLEKHA3 genes. PLEKHA3 has not been associated with a known condition at this time. TTN, however, is expressed in the skeletal and cardiac muscles and has been associated with several conditions including isolated cardiomyopathies, limb-girdle muscular dystrophy, proximal myopathy with early respiratory involvement, Salih myopathy, and Tibial muscular dystrophy. The deletion includes exons 229-313 of the TTN gene. This deletion includes the A and M bands of the protein and this particular deletion has not been reported previously. Deletions and loss of function variants in TTN that impact the A and M bands, such as the deletion found in this patient, are associated with isolated cardiomyopathies. 18-25% of dilated cardiomyopathies have been associated with such TTN variants. Deletions such as this have also been detected in healthy individuals (Herman et al. 2012). This could be due to reduced penetrance, however. The variant was also detected in the patient's mother who does not have a reported history of cardiomyopathy. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677987 | SCV000804142 | uncertain significance | not provided | 2018-02-01 | criteria provided, single submitter | provider interpretation | This 468 kilobase deletion was identified in a male with a history of mild intellectual disability and autism spectrum disorder. The deletion includes four genes, two of which (FANF and ANO5) are associated with a clinical disorder via autosomal recessive or dominant negative mechanisms. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677988 | SCV000804143 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This deletion was identified in a patient with a history of developmental delay, learning disorder, articulation disorder, stereotypic movements, and ADHD. The deletion overlaps with the Williams-Beuren critical region but does not include the ELN gene. The effect of this deletion is unclear. The patient also carries a 22q11.21 duplication and both copy number variants were found to be paternally inherited. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677989 | SCV000804144 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 625 kilobase duplication was identified in an individual with a history autism and global developmental delay/intellectual disability. This duplication includes 15 genes, none of which are known to be triplosensitive at this time. This duplication was also identified in the patient's mother who reportedly has a history of speech and learning delays, asthma, and reflux. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677990 | SCV000804145 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | provider interpretation | This 98 kilobase duplication was identified in a patient with a history of learning disability, large stature, and overgrowth. The duplication includes ANKRD11 and SPG7 genes. These genes are associated with autosomal dominant KBG syndrome and spastic paraplegia type 7, respectively, but the effect of a duplication involving these genes is unclear. Copy number variation in this region has been reported in the general population. The duplication was detected in the patient's mother who does not have a reported history of neurodevelopmental concerns and is of typical stature. Additional genetic testing, including whole exome sequencing, has been performed and has not yieled an explanation for the patient's phenotype. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677991 | SCV000804146 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old female with autism spectrum disorder and speech delay. The duplication was also found to be maternally inherited. Nonsense variants and deletions of SHOX have been reported in individuals with idiopathic short stature and Leri-Weill dyschondrosteosis (Huber et al. 2001; Niesler et al. 2002; Rappold et al. 2002). Partial or complete duplications of SHOX and/or its enhancer regions have also been reported in patients with these conditions (Thomas et al. 2009; Benito-Sanz et al. 2011). Tall stature has also been reported with duplications. This patient and her mother are of typical height. Whole exome sequencing also identified a variant of uncertain significance in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677992 | SCV000804147 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | provider interpretation | This 421 kilobase duplication was identified in a female with a history of short stature, ADHD, developmental language disorder, and borderline delays in visual-motor/problem-solving adaptive skills. Similar duplications that involve the ARX gene have been reported in males in the literature. Two males had developmental delay and intellectual disability while two others had typical intelligence, causing the authors to postulate that another genetic varaint explained or contributed to the two patients' neurodevelopmental phenotype (Popoviel et al. 2014). A likely pathogenic 22q11.21 atypical deletion was also identified in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677993 | SCV000804148 | likely pathogenic | not provided | 2018-03-27 | criteria provided, single submitter | provider interpretation | This 412 kilobase deletion was identified in an 11 year old patient with a history of intellectual disability, autism spectrum disorder, amblyopia, and congenital pes planus. Copy number variants of Xq28 have been associated with intellectual disability in males. Females in the literature have been reportedly asymptomatic due to skewed X-inactivation. X-inactivation studies for this patient demonstrated completely skewed X-inactivation (100:0). Similar deletions have been reported in the literature and are thought to be embryonic lethal in males (El-Hattab 2011; El-Hattab 2015). A likely benign 19p13.2 duplication was also identified, and parental testing indicated that the Xq28 deletion was maternally inherited. This patient's mother has a history of 3 miscarriages. Given the skewed X-inactivation in this patient, this deletion does not explain her neurodevelopmental phenotype. The deletion is likely associated with the mother's increased risk for miscarriage. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677994 | SCV000804149 | pathogenic | not provided | 2018-03-27 | criteria provided, single submitter | provider interpretation | This 2.6 Mb deletion was identified in a 10 year old male with a history of autism spectrum disorder, intellectual disability, and ADHD. Overlapping deletions of 15q24.1q24.2 have been identified in individuals with developmental delay, intellectual disability, dysmorphic features, hypotonia, digital anomalies, joint laxity and genital anomalies (Mefford et al. 2012; El-Hattab et al 2009; Van Esch et al. 2009). In the literature, deletions were de novo in each case. Parental follow-up testing has not been completed for this family to date. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677995 | SCV000804150 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | provider interpretation | This 1.6 Mb deletion was identified in a 16 year old male with a history of migraines, autism spectrum disoder, and anxiety. Maternal inheritance has been ruled out, but paternal testing has not been completed to date. A pathogenic 16p11.2 duplication was also identified in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677996 | SCV000804151 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This 41 kilobase deletion was identified in a 15 year old with a history of mild intellectual disability, speech and language disorder, and ADHD. The deletion includes a portion of the TPRX1 gene and the entire CRX gene. Deletions and loss of function variants in CRX have been associated with Leber congenital amaurosis 7, cone-rod dystrophy 2, and late-onset retinitis pigmentosa. Aside from a history of strabismus, the patient does not have a history of vision concerns. This deletion was determined to be maternally inherited. The patient's mother does not have a reported history of vision concerns. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677997 | SCV000804152 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This 156 kilobase duplication was identified in a 7 year old with a history of intellectual disability, autism spectrum disorder, pica, hyperkinesis, sleep disturbance, and polyuria. The duplication was found to be maternally inherited. The duplicated region includes a portion of the UPRT and ZDHHC15 genes. A loss of function variant in ZDHHC15 has been reported in an individual with intellectual disability (Manosouri et al. 2015), but the impact of a duplication of this variant is unclear. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677998 | SCV000804153 | pathogenic | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This approximately 2.2 Mb deletion was identified in a 13 year old female with a history of autism spectrum disorder, intellectual disability, and disruptive behavior. The deleted region includes 4 genes, including FOXP2. Loss of function FOXP2 variants are associated with speech and language disorders (Watkins et al 2002; Laffin et al. 2012; Fedorenko et al. 2016). Parental testing has not been completed to date. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000677999 | SCV000804154 | uncertain significance | not provided | 2018-04-03 | criteria provided, single submitter | provider interpretation | This 323 kilobase duplication was identified in a male with a history of obesity, acanthosis nigricans, mixed receptive-expressive language disorder, motor stereotypy. The duplication includes 15 genes, but none are known to be triplosensitive. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678000 | SCV000804155 | uncertain significance | Mitochondrial complex I deficiency | 2018-03-28 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 6 year old female with microcephaly, history of developmental delays, Duane's syndrome, and alopecia. Parental testing was not completed. This deletion includes 10 genes including, STRN3, CPR33, ARGHAP5, NUBPL, and APA4S1. NUBPL sequencing and del/dup was negative for any additional changes in this gene. Individuals with deletions of NUBPL are typically asymptomatic carriers for complex 1 defiencicy. The clinical significance of this deletion is unknown. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678001 | SCV000804156 | uncertain significance | not provided | 2018-03-28 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old female with global developmental delay, mild dysmorphic features, and esotropia. Parental testing was not completed. This deletion included a portion of the gene AUTS2. Additionally, a variant of uncertain significance in the LRRC7 gene was identified through whole exome sequencing. The clinical significance of this duplication remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678002 | SCV000804157 | uncertain significance | not provided | 2018-03-28 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 9 year old male with language disorder, mild intellectual disability, mild hypotonia, disruptive behavior, sleep problems, and a history of global developmental delay. Parental testing was not completed. This duplication includes ten genes, three of which are associated with known clinical disorders; LRRK2, CNTN1, and PRICKLE1. The clinical significance of this duplication remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678003 | SCV000804158 | uncertain significance | not provided | 2018-03-28 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 8 year old male with autism spectrum disorder, ADHD, and unspecified cognitive abilities. Parental testing was not completed. This duplication includes a portion of two genes, FSCN2 and RAAP100. The clinical consequences of a partial duplication of FSCN2 and FAAP100 remain unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678004 | SCV000804159 | uncertain significance | Autistic disorder | 2018-03-28 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 13 year old male with autism spectrum disorder, intellectual disability, bipolar disorder, conduct disorder, periventricular leukomalacia, and asthma. Parental testing was not completed. This deletion includes a portion of CNTN4. Disruptions of CNTN4 have been reported in individuals with autism spectrum disorders, individuals with 3p- syndrome, and unaffected parents. It is not clear whether this deletion is related to the patient's neurodevelopmental history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678005 | SCV000804160 | likely pathogenic | Parkinson disease 2 | 2018-03-01 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 3 year old male with bilateral intra-abdominal testicle, hypertelorism, conductive hearing loss, exotropia, global developmental delay, echogenic kidneys, abnormality of gait, and hyperkinesis. Parental testing was not completed. This deletion includes a portion of PARK2. Individuals with deletions of PARK2 are typically asymptomatic carriers for juvenile onset Parkinson Disease. There is a maternal family history of Parkinson Disease that onset before 30 years of age. This deletion does not explain the findings in this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678006 | SCV000804161 | uncertain significance | not provided | 2018-03-28 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 18 year old female with autism spectrum disorder, ADHD, and epilepsy. Parental testing was not completed. This deletion includes a portion of TMEM132C and the entirity of TMEM132B, SLC15A4, and GLT1D1, none of which are associated with a known clinical disorder at present. The clinical significance of this deletion remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678007 | SCV000804162 | uncertain significance | Epilepsy, focal, with speech disorder and with or without mental retardation | 2018-03-28 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with macrocephaly, speech delay, autism spectrum disorder, large ears, and developmental delays, and was maternally inherited. Patient's mother has a history of anxiety, with a family history of depression, learning disabilities, and seizures. This duplication includes a portion of GRIN2A, which is associated with focal epilepsy and speech disorder with or without intellectual disability for heterozygous variants. However the clinical signifiance of this duplication is not known at this time. A maternally inherited variant of uncertain significance in the TB1X gene was also identified through whole exome sequencing. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678008 | SCV000804163 | uncertain significance | not provided | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 10 year old female with nonintractable epilepsy with simple partial seizures, short stature, intellectual disability, and MRI brain abnormalities, and was maternally inherited. Patient's mother has a history of bipolar disorder and depression. This deletion contains 13 genes, including six OMIM genes: PTPN12, MAGI2, GNAI1, GNAT3, CD36, and SEMA3C. Individuals with varaints in CD36 are typically asymptomatic carriers for platelet glycoprotein IV deficiency. The clinical significance of this deletion beyond carrier status remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678009 | SCV000804164 | uncertain significance | not provided | 2018-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 3 year old male with global developmental delays and a mixed receptive-expressive language disorder, and was found to be paternally inherited. Proband's father is reportedly unaffected, with no history of developmental delays. This duplication includes a portion of CBX7 and RPL3 genes, and the entirety of PDGFB. The clinical significance of a duplication of these genes is not currently known. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678010 | SCV000804165 | uncertain significance | Autistic disorder | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 7 year old male with developmental speech disorder, disruptive behavior disorder, hypermetropia, constipation, ADHD, dysmorphic features, and a history of failure to thrive. Parental testing was not completed. This deletion includes a portion of CNTN4 and is within the larger distal 3p deletion syndrome region. CNTN4 is a candidate gene for autism spectrum disorders. The clinical significance of this deletion remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678011 | SCV000804166 | uncertain significance | Acrodysostosis 2, with or without hormone resistance | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 10 year old male with autism spectrum disorder, macrocephaly, some hyperpigmented patches, some joint hypermobility, and anxiety. This deletion was also identified in the proband's twin brother who is similarly affected, but parental testing was not completed. This deletion includes three genes, including PDE4D , and is within the region for the much larger 5q12.1 deletion syndrome. The clinical significance of a deletion of these genes is not currently known. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678012 | SCV000804167 | likely pathogenic | not provided | 2018-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 11 year old male with intellectual disability, autism spectrum disorder, ADHD, and a seizure disorder. Parental testing was not completed. This duplication includes 18 OMIM genes and 31 other genes. Identical duplications have not been reported, though overlapping duplications have been noted in DECIPHER in individuals with autism, intellectual disability, seizures, and dysmorphic features. Due to the size of this duplication, it is likely the explanation for this patient's presentation. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678013 | SCV000804168 | pathogenic | Breast-ovarian cancer, familial 1 | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 4 year old male with global developmental delays, macrocephaly, and craniosynostosis. Parental testing was not completed and there was a strong maternal family history of breast and ovarian cancer. This deletion includes BRCA2 and explains this family history, but is likely non-contributory to the proband's medical and developmental history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678014 | SCV000804169 | uncertain significance | Leri-Weill dyschondrosteosis | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 7 year old male with autism spectrum disorder and mild intellectual disability. Parental testing was not completed. This deletion is within the pseudoautosomal region on the short arm terminus of both chromosome X and Y, and involves SHOX enhancers. Of note, this patient is of normal height. Similar deletions have been seen in patients with microcephaly, developmental delays, and/or speech delays. The clinical signifiance of this deletion is currently unclear. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678015 | SCV000804170 | pathogenic | Mental retardation, autosomal recessive 7 | 2018-03-30 | criteria provided, single submitter | provider interpretation | This homozygous deletion was identified in a 6 year old male with global developmental delays, short stature, chiari malformation type I, exotropia, and microcephaly. Microarray showed 5-6% homozygosity. Analysis of a maternal sample confirmed she is a heterozygous carrier for this deletion. This deletion includes at least exons 2-6 of TUSC3, which is associated with an autosomal recessive form of intellectual disability. This deletion explains the neurodevelopmental phenotype of this patient. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678016 | SCV000804171 | uncertain significance | Pigmented nodular adrenocortical disease, primary, 2 | 2018-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 9 year old male with history of global developmental delay, unspecified intellectual disability, ADHD, and esotropia. This patient also has a 15q11.2 deletion that is a known recurrent deletion associated with neurodevelopmental phenotypes and is believed to be the cause of this patient's symptoms. Parental testing was not completed for either variant, though there is a maternal family history for the 15q11.2 deletion. This duplication involves a portion of PDE11A. The clinical significance of the duplication of a portion of this gene is unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678017 | SCV000804172 | uncertain significance | not provided | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 19 year old female with mild intellectual disability, ADHD, anxiety, and hyperphagia, and was found to be de novo. This patient has had normal whole exome sequencing. This deletion includes no genes that are associated with a known clinical phenotype at present. It is unclear at this time if this deletion is related to the patient's neurodevelopmental history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678018 | SCV000804173 | uncertain significance | Witteveen-kolk syndrome | 2018-03-30 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 12 year old male with autism spectrum disorder, dysmorphic features, ADHD, a patent foramen ovale, and intellectual disability. Parental testing was not completed. This duplication includes 10 genes, including SIN3A. This duplication is within the 15q24 region, and similar duplications have been reported in patients with a similar phenotype to the recurrent deletion. The clinical significance of this duplication remains unclear. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678019 | SCV000804174 | uncertain significance | not provided | 2018-03-30 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 8 year old male with autism spectrum disorder, ADHD, and obesity. Parental testing was not completed. This deletion contains the non-coding exon 1 of RBFOX1. Deletions within RBFOX1 have conflicting reports of clinical significance ranging from causing epilepsy and autism spectrum disorders to being normal variation. The clinical significance of the deletion of a portion of this gene is remains unclear. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678021 | SCV000804176 | pathogenic | not provided | 2018-04-02 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 16 year old male with intellectual disability, seizure disorder, irritability, submucosal cleft palate, microcephaly, short stature, sleep disturbances, and Emery-Driefuss muscular dystrophy. Parental testing was not completed. This region contains at least 36 genes and was also identified on a karyotype. A 16p13.11 intragenic deletion of ABCC6 was also identified through array and a FHL1 likely pathogenic variant identified through a HCM gene panel. Due to its size, this deletion is believed to explain this patient's neurodevelopmental history in combination with his FHL1 mutation. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678022 | SCV000804177 | uncertain significance | not provided | 2018-04-12 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old male with microcephaly, dysmorphic features (large ears, close set eyes, pointed chin), behavioral concerns, pica, myopia, astigmatism, and was found to be maternally inherited. This patient's mother has a history of learning problems and a bicornuate uterus, and a family history of ADHD, special education needs, schizophrenia, depression, deafness, and substance abuse. This duplication includes 18 genes, including MYO9B, CPAMD8, and GTPBP3. The clinical significance of the duplication of these genes remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678023 | SCV000804178 | pathogenic | Pitt-Hopkins-like syndrome 2 | 2018-04-12 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 17 year old male with autism spectrum disorder, intellectual disability, ADHD, aggression, constipation, and weight loss. Parental testing was not completed. This deletion includes a portion of NRXN1, and similar other deletions are have been reported in individuals with autism, intellectual disability, ADHD, schizophrenia, and/or seizures. Biallelic mutations in NRXN1 are associated with Pitt-Hopkins-like syndrome 2. Of note this patient does not have hyperbreathing, developmental regression, or facial dysmorphism. This deletion appears to explain the patient's medical history. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678024 | SCV000804179 | uncertain significance | Deafness, autosomal dominant 56 | 2018-04-12 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 13 year old male with learning disabilities, ADHD, articulation disorder, and mild dysmorphic features, and was maternally inherited. The patient's mother has a history of depression, anxiety, and five first trimester miscarriages. This duplication includes the entirity of TNC and DEC1, and a portion of PAPPA and TNFSF8. There is no family history of hearing loss. The clinical significance of carrying three copies of these genes is unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678025 | SCV000804180 | uncertain significance | Familial hypertrophic cardiomyopathy 16 | 2018-04-12 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 10 year old male with intellectual disability, macrocephaly, autism spectrum disorder, hyperkinesis, sleep disturbances, and hypodontia. Parental testing was not completed. This duplication includes the gene MYOZ2, which is associated with hypertrophic cardiomyopathy. There is one overlapping duplication reported in the literature that includes two additional genes in a patient with Cantu syndrome. The clinical significance of this duplication remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678026 | SCV000804181 | uncertain significance | Usher syndrome, type 2A; Retinitis pigmentosa 39 | 2018-04-12 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 9 year old male with autism spectrum disorder, and a history of ADHD and developmental delays. Parental testing was not completed. This duplication includes two genes, KCTD3 and USH2A. Of note this patient is negative for hearing loss or retinitis pigmentosa. The clinical significance of this duplication remain unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678027 | SCV000804182 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2K | 2018-04-13 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 3 year old female with receptive-expressive language disorder, premature birth, hypotonia, poor feeding, posteriorly rotated ears, and up-slanting palpebral fissures, and is maternally inherited. This deletion includes six genes, including TMEM70, GDAP1, and JPH1. Individuals with single variants in TMEM70 are typically asymptomatic carriers for mitochondrial complex V deficiency. GADP1 and JPH1 have been described to cause an autosomal dominant Charcot-Marie-Tooth disease type 2K with muscle weakness and atrophy. Patient's mother reportedly has similar facial features and short stature, though no muscle concerns reported. The clinical significance of this deletion remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678028 | SCV000804183 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 7 year old female with short stature, macrocephaly, intellectual disability, global developmental delays, dysmorphic features (midface hypoplasia, high forehead, periorbital fullness, thick eyebrows, broad nasal root, low nasal bridge, up-turned nasal tip, short philtrum, full lips, wide mouth, pointed chin), decreased motor strength, joint hyperflexibility, increased lordosis, hyperextensible joints, flat feet, and was found to be maternally inherited. This patient's mother has anxiety, asthma, required learning supports, and had a heart murmur. Mother and maternal grandmother reportedly had a history of infertility. This deleted region contains three genes (RPS6KC1, VASH2, ANGEL2) that are not associated with any known clinical disorders. The clinical significance of this deletion remains unclear at this time. A second maternally-inherited variant was identified through chromosomal microarray, a 10q23.1 duplication of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678029 | SCV000804184 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 7 year old female with short stature, macrocephaly, intellectual disability, global developmental delays, midface hypoplasia, high forehead, periorbital fullness, thick eyebrows, broad nasal root, low nasal bridge, up-turned nasal tip, short philtrum, full lips, wide mouth, pointed chin, decreased motor strength, joint hyperflexibility, increased lordosis, hyperextensible joints, flat feet, and was found to be maternally inherited. This patient's mother has anxiety, asthma, required learning supports, and had a heart murmur. Mother and maternal grandmother reportedly had a history of infertility. This duplicated region contains six regions, including CDHR1, RGR, and a portion of CCSER2. The clinical significance of carrying three copies of these genes is unclear at this time. A second maternally inherited variant was identified through chromosomal microarray, a 1q32.3 deletion of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678030 | SCV000804185 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 3 year old female with autism spectrum disorder, overgrowth, macrocephaly, fine motor delay and speech delay, and was maternally inherited. This patient's mother has average cognitive abilities and has anxiety, depression, and OCD. This duplication includes a portion of VCX3A and VCX2, and the entirety of HDHD1, STS, VCX, and PNPLA4. Identical duplications in this region have been reported with conflicting reported pathogenicity (benign-pathogenic) in individuals with features including developmental delay, seizures, autism spectrum disorder, and intellectual disability. The clinical significance of three copies of these genes remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678031 | SCV000804186 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 9 year old male with intellectual disability, gross motor delay, infantile benign external hydrocephaly, ADHD, overweight, and sleep difficulties, and was paternally inherited. This patient's father has bipolar and intellectual disability. This deletion includes ADARB2 and a portion of WDR37. Neither of these genes is associated with a known clinical disorder at present. Overlapping deletions have been seen in individuals with developmental delay or dysmorphic features, with some including the gene ZMYND11 that is known to cause intellectual disability. The clinical significance of this deletion remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678033 | SCV000804188 | uncertain significance | not provided | 2018-04-16 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 5 year old male with overgrowth, developmental regression, speech delay, autism spectrum disorder, with history of an EEG with paroxysmal discharges that were considered epileptiform, and a brain MRI that noted scattered foci of T2 hyperintensity in the cerebral white matter bilaterally. Parental testing was not completed. This duplication contains seven genes, including GCSH, and a portion of an eighth gene. The clinical significance of three copies of these genes remains unclear at this time. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678034 | SCV000804189 | pathogenic | Spinocerebellar Ataxia Type 15 | 2018-04-16 | criteria provided, single submitter | provider interpretation | This deletion was identified in a 4 year old male with global developmental delays, seizures, hypermetropia of both eyes, amblyopia of right eye, hemangioma, dysmorphic features (triangular facies, broad forehead, prominent crus, almond shaped eyes, thick eyebrows, hypoplastic alae, prominent nasal tip, thin lips, narrow palate, pointed chin, decreased motor strength), partial agenesis of the corpus callosum, and prenatal exposure to cigarettes. Parental testing was not completed for the patient's father and the patient's mother tested negative. This deletion contains two genes SUMF1 and SETMAR, and a portion of ITPR1. Heterozygous carriers of SUMF1 variants are most often asymptomatic carriers for multiple sulfatase deficiency. Deletions of ITPF1 have been shown to cause spinocerebellar ataxia type 15. Microarray also identified a likely pathogenic duplication at 13q13.3. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678035 | SCV000804190 | likely pathogenic | not provided | 2018-04-16 | criteria provided, single submitter | provider interpretation | This duplication was identified in a 4 year old male with global developmental delays, seizures, hypermetropia of both eyes, amblyopia of right eye, hemangioma, dysmorphic features (triangular facies, broad forehead, prominent crus, almond shaped eyes, thick eyebrows, hypoplastic alae, prominent nasal tip, thin lips, narrow palate, pointed chin, decreased motor strength), partial agenesis of the corpus callosum, and prenatal exposure to cigarettes. Parental testing was not completed for the patient's father and the patient's mother tested negative. This duplication contains two genes, MIR17HG and GPC5, and a portion of GPC6. Similar duplications including MIR17HG and a portion of GPC5 have been reported in two individuals: one with postaxial polydactyly, overgrowth, autistic features, and dysmorphic features and was inherited from a similarly affected mother, and in a patient with developmental delay, autism spectrum disorder, short stature, macrocephaly, brachydactyly, clinodactyly, and dysmorphic features that was also identified in a parent and sibling with similar features. This duplication likely contributes to the phenotype of this patient. Microarray in our patient also identified a pathogenic deletion at 3q26.1, which is associated with spinocerebellar ataxia type 15. |
| Daryl Scott Lab, |
RCV000681464 | SCV000808912 | pathogenic | Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart | 2017-09-12 | criteria provided, single submitter | clinical testing | |
| Medical Genetics Lab, |
RCV000681666 | SCV000809058 | uncertain significance | Intellectual disability, mild | 2018-09-27 | criteria provided, single submitter | clinical testing | This is a homozygous deletion that involves only the BTBD9 gene, identified in a patient with mild intellectual disability, microcephaly, mild dismorphism. Parents are healthy, second-degree cousins of Italian origin, and are heterozygous carriers of the deletion. A healthy brother is also heterozygous. BTBD9 has not been currently associated to any monogenic disorder in humans, but it is expressed in brain and is a good candidate for neurodevelopmental disorders. |
| Undiagnosed Diseases Network, |
RCV000708570 | SCV000837689 | pathogenic | Cornelia de Lange syndrome 5 | 2018-03-16 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV000708593 | SCV000837720 | likely pathogenic | Combined oxidative phosphorylation deficiency 31 | 2018-01-04 | criteria provided, single submitter | clinical testing | |
| Genetics - |
RCV000722071 | SCV000845782 | pathogenic | Split-hand/foot malformation | 2018-10-31 | criteria provided, single submitter | clinical testing | Duplications of this region are associated with split hand/foot malformation 3. |
| Genetics - |
RCV000722072 | SCV000845790 | pathogenic | Split-hand/foot malformation | criteria provided, single submitter | clinical testing | Duplications of this region are associated with split hand/foot malformation 3. | |
| Eurofins NTD LLC |
RCV000730072 | SCV000857783 | uncertain significance | not provided | 2017-10-24 | criteria provided, single submitter | clinical testing | |
| Eurofins NTD LLC |
RCV000734617 | SCV000862771 | other | not provided | 2018-08-06 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV000735205 | SCV000863411 | uncertain significance | Branched-chain keto acid dehydrogenase kinase deficiency | 2018-03-16 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV000735209 | SCV000863416 | likely pathogenic | TAX1BP3-related arrhythmogenic right ventricular cardiomyopathy | 2018-11-27 | criteria provided, single submitter | clinical testing | A hemizygous c.233T>C (p.M78T) variant in the TAX1BP3 gene was detected in three brothers (14yo male, 20yo male, and male that died suddently at age 17) with similar symptoms. Exome sequencing showed that all three brothers are hemizygous, the mother is heterozygous, and the father is negative for this change. Concurrent array analysis revealed a heterozygous copy number loss of approximately 238 Kb in size (genomic position chr17:3394299- 3632836) in all three brothers. This large deletion encompasses the entire TAX1BP3 gene. SNP arrays detected this deletion as heterozygous in all three brothers and the father. The mother is negative for the deletion. Therefore, the 238 Kb deletion and the c.233T>C (p.M78T) variant are located on two chromosomes (in trans configuration). We believe the combination of the missense variant and deletion in trans is likely pathogenic. |
| Undiagnosed Diseases Network, |
RCV000735211 | SCV000863419 | pathogenic | Early infantile epileptic encephalopathy 4 | 2017-10-23 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV000735212 | SCV000863420 | pathogenic | Deafness-infertility syndrome | 2017-11-14 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV000735214 | SCV000863422 | pathogenic | Charcot-Marie-Tooth disease, type IA | 2018-06-26 | criteria provided, single submitter | clinical testing | 1.4Mb pathogenic copy number gain on chromosome 17 at 17p12. Detected by chromosomal microarray. |
| Undiagnosed Diseases Network, |
RCV000735229 | SCV000863438 | pathogenic | Wieacker-Wolff syndrome | 2017-06-15 | criteria provided, single submitter | clinical testing | 95 kb deletion includes coding exon 1 which explains X-linked pathogenicity. Carrier females may have mild features of Wieacker-Wolff syndrome compared to hemizygous males. |
| Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV000785663 | SCV000863549 | uncertain significance | Silver Russell Syndrome-related disorder | 2018-12-06 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735898 | SCV000864010 | uncertain significance | Trichorhinophalangeal dysplasia type I | 2018-12-17 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735899 | SCV000864011 | uncertain significance | Trichorhinophalangeal dysplasia type I | 2018-12-17 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735900 | SCV000864012 | pathogenic | Trichorhinophalangeal dysplasia type I | 2018-12-17 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735901 | SCV000864013 | pathogenic | Hypoparathyroidism, deafness, renal disease syndrome | 2018-12-17 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735904 | SCV000864016 | uncertain significance | Cerebellar ataxia, nonprogressive, with mental retardation | 2018-12-17 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735905 | SCV000864017 | benign | Cerebellar ataxia, nonprogressive, with mental retardation | 2018-12-17 | criteria provided, single submitter | research | |
| Rare Disease Group, |
RCV000735906 | SCV000864018 | uncertain significance | Cerebellar ataxia, nonprogressive, with mental retardation | 2018-12-17 | criteria provided, single submitter | research | |
| Raymond Lab, |
RCV000850220 | SCV000897737 | pathogenic | Intellectual disability | 2019-02-13 | criteria provided, single submitter | research | |
| Department of Clinical Genetics, |
RCV000768549 | SCV000898485 | pathogenic | Dihydropteridine reductase deficiency | 2019-04-20 | criteria provided, single submitter | research | |
| Biochemistry Laboratory of CDMU, |
RCV000768460 | SCV000899223 | likely pathogenic | not provided | criteria provided, single submitter | case-control | ||
| NIHR Bioresource Rare Diseases, |
RCV000852264 | SCV000900011 | likely pathogenic | Hereditary factor IX deficiency disease | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852268 | SCV000900013 | likely pathogenic | Reduced antithrombin III activity | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852266 | SCV000900014 | likely pathogenic | Hereditary factor X deficiency disease | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852267 | SCV000900015 | likely pathogenic | Abnormal bleeding | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852274 | SCV000900016 | uncertain significance | Abnormal bleeding | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852258 | SCV000900022 | likely pathogenic | 11q partial monosomy syndrome | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852273 | SCV000900024 | pathogenic | Macrothrombocytopenia | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852269 | SCV000900025 | likely pathogenic | Thrombocytopenia | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852261 | SCV000900027 | likely pathogenic | Reduced antithrombin III activity | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852271 | SCV000900030 | likely pathogenic | Deep venous thrombosis | 2019-02-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000852272 | SCV000900031 | likely pathogenic | Protein S deficiency disease | 2019-02-01 | criteria provided, single submitter | research | |
| Undiagnosed Diseases Network, |
RCV000786772 | SCV000924629 | likely pathogenic | 1p13.3 deletion syndrome | 2019-06-06 | criteria provided, single submitter | clinical testing | Both loss- and gain-of-function mutations in the KCNA2 gene cause early infantile epileptic encephalopathy-32 (EIEE-32; # 616366) (Allen, et al. Epilepsia. 2016 Jan;57(1):e12-7.). EIEE causes severe epilepsy with variable types of seizures, and neurological deficits, including intellectual disability, and delay of psychomotor and language development. Ataxia, tremor, and myoclonus have also been associated with EIEE. The onset of seizures has been reported to typically occur at less than five years of age and may remit later in childhood, however, one individual with a deletion involving all of the KCNA2 gene was reported to have onset of generalized tonic-clonic seizures at the age of 14 along with intellectual disability (Lal, et al. PLoS Genet. 2015 May 7;11(5):e1005226.) Within this deletion, two other genes, SLC25A24 and GNAI3 have been associated with autosomal dominant disorders. Mutations in SLC25A24 have been associated with Gorlin-Chaudhry-Moss syndrome and Fontaine progeroid syndrome (FPS, OMIM #612289), which have overlapping clinical features. Several studies suggest that the SLC25A24 mutations for these indiviudals induce a gain of function. Mutations of GNAI3 have been identified in patients with auriculocondylar syndrome-1 (ARCND1 or ACS, OMIM #602483), and it is thought that ACS is not caused by GNAI3 haploinsufficiency. For both of these disorders, whole gene deletions would not be expected to result in the same mechanism or clinical features of these disorders. Additionally, six genes are associated with autosomal recessive conditions, for which this deletion likely infers a carrier status. Chudley-McCullough syndrome (CMCS; #604213) is caused by homozygous or compound heterozygous mutation in the GPSM2 gene, while autosomal recessive mental retardation-60 (MRT60; # 617432) and autosomal recessive mental retardation-48 (MRT48; #616269) are caused by mutations in the TAF13 and SLC6A17 genes, respectively. Pontocerebellar hypoplasia type 9 (PCH9; #615809) is caused by mutations in both copies of the AMPD2 gene and frontonasal dysplasia-1 (FND1; OMIM #136760), are caused by mutations in both copies of the ALX3 gene. |
| Undiagnosed Diseases Network, |
RCV000754630 | SCV000930559 | pathogenic | Kilquist syndrome | 2019-01-01 | criteria provided, single submitter | clinical testing | Homozygous deletion of SLC12A2 due to uniparental paternal isodisomy. Deletion from intron 1 to the beginning of exon 7 (chr5:127441491†127471419) including an inversion of 34 base pairs (chr5:127441491â€127471419delins34). As a carrier, the father shows no symptoms of Kilquist syndrome. This family has been reported in PMID: 30740830. |
| Undiagnosed Diseases Network, |
RCV000791288 | SCV000930566 | likely pathogenic | Kleefstra syndrome 2 | 2017-12-15 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000824954 | SCV000965989 | pathogenic | Intellectual disability, severe | 2016-01-01 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000824957 | SCV000965998 | pathogenic | Marfan syndrome | 2016-01-01 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000825024 | SCV000966219 | pathogenic | Leptin receptor deficiency | 2018-07-17 | criteria provided, single submitter | clinical testing | Observed as a homozygote. |
| Equipe Genetique des Anomalies du Developpement, |
RCV000825026 | SCV000966221 | pathogenic | Chromosome 15q11-q13 duplication syndrome | 2018-10-16 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000825598 | SCV000966941 | likely pathogenic | Lynch syndrome | 2018-04-27 | criteria provided, single submitter | clinical testing | This MSH2 variant is a deletion encompassing exons 8 to 15, though it should be noted that its exact breakpoints cannot be determined due to limitations of the testing methodology. This multi-exon deletion has been reported in 1 individual with Lynch syndrome and 1 individual referred for hereditary cancel panel testi ng at a diagnostic laboratory (Liu 1994, Susswein 2015) and has also been report ed by another clinical laboratory in ClinVar (Variation ID# 417806). Deletions w ithin exons 8 to 15 as well as larger deletions spanning these exons have been r eported in multiple individuals with colorectal cancer in the Human Gene Mutatio n Database (HGMD: Stenson 2017). This deletion is predicted to result in a prema ture stop codon in the last exon on the MSH2 gene (exon 16), and while it is mor e likely to escape nonsense mediated decay, it is expected to result in a trunca ted protein where approximately half of the MSH2 coding sequence is removed. In summary, although additional studies are required to fully establish its clinica l significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PV S1_strong, PM2. |
| Laboratory for Molecular Medicine, |
RCV000825957 | SCV000967442 | uncertain significance | not specified | 2018-10-29 | criteria provided, single submitter | clinical testing | This deletion encompasses MIR96; however, please note that the exact breakpoints of this deletion could not be determined by this assay. Several multi-gene dele tions encompassing MIR96 have been reported in individuals with developmental de lay and other features in the DECIPHER database, however hearing loss was not re ported for any of these individuals and the deletions reported impacted >200 gen es (https://decipher.sanger.ac.uk). Recurrent smaller deletions encompassing onl y the miR-183/182/96 cluster and the 3? end of an adjacent gene (NRF1) have been reported in dbVar in several control population studies with one study reportin g a MAF of 0.3% (12/4052 alleles) in healthy controls (Shaikh 2009), which sugge st that the loss of MIR96 is not likely to be disease causing. However, due to t he technical limitation of this assay in detecting the breakpoints and length of this deletion, the impact of this deletion on neighboring disease-relevant gene s cannot be determined. In summary, although loss of MIR96 is not expected to be related to hearing loss, due to uncertainty regarding the size and breakpoints of the deletion, the clinical significance of this deletion is uncertain. ACMG/A MP criteria applied: none. |
| Laboratory for Molecular Medicine, |
RCV000826027 | SCV000967517 | uncertain significance | not specified | 2018-04-12 | criteria provided, single submitter | clinical testing | The c.(?_-15)_(1947_?)dup variant in RAF1 is a duplication of the coding exons: exons 2-17. The exact breakpoints of this gain cannot be determined by this meth od, and exon 1 is not included in the test as it is non-coding. Gains of the RAF 1 gene, including large CNVs that include RAF1 and other genes, have been report ed in several individuals with variable phenotypes as well as in healthy control s. Large CNVs encompassing RAF1 and additional genes been reported in one indivi dual with TOF and two individuals with varying phenotypes and severity, one of w hich was inherited from an unaffected father (Silversides 2012, Luo 2012, Lissew ski 2015). Whole gene gains of RAF1 have also been reported in 3 individuals in Decipher (http://decipher.sanger.ac.uk/) with ID and other phenotypes, two of wh ich were inherited from an unaffected parent. Large CNVs encompassing RAF1 and a dditional genes has been reported as uncertain in ClinVar, in ten individuals in the Database of Genomic Variants (DGV, http://dgv.tcag.ca), and in 3/41234 tota l chromosomes in Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org). In summary, the clinical significance of this partial gain of the RAF1 gen e is uncertain. |
| Laboratory for Molecular Medicine, |
RCV000826068 | SCV000967562 | uncertain significance | not specified | 2018-03-23 | criteria provided, single submitter | clinical testing | The duplication of exons 192-244 in TTN has not been previously reported in indi viduals with cardiomyopathy. It is unknown if this duplication is in tandem, wit h the possibility of altering protein expression/function, or was inserted in a different locus, which may not impact the protein. A similar duplication, involv ing exons 193-244, was identified by our laboratory in one individual with DCM. A larger intragenic duplication involving this region was identified in one cont rol sample (Kidd 2008). In summary, the clinical significance of this duplicatio n is uncertain. |
| Academic Department of Medical Genetics, |
RCV000850066 | SCV000992232 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-26 | criteria provided, single submitter | research | |
| Academic Department of Medical Genetics, |
RCV000850067 | SCV000992233 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-26 | criteria provided, single submitter | research | |
| Academic Department of Medical Genetics, |
RCV000850068 | SCV000992234 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-26 | criteria provided, single submitter | research | |
| Academic Department of Medical Genetics, |
RCV000850149 | SCV000992322 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-26 | criteria provided, single submitter | research | |
| Academic Department of Medical Genetics, |
RCV000850150 | SCV000992323 | pathogenic | Hereditary leiomyomatosis and renal cell cancer; Hereditary cancer-predisposing syndrome | 2018-01-26 | criteria provided, single submitter | research | Observed in an individual with phenotype specific for variants in one of the deted genes |
| Wong Mito Lab, |
RCV000850756 | SCV000992989 | benign | Juvenile myopathy, encephalopathy, lactic acidosis AND stroke | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.4388A>G variant in MT-TQ gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4, BP4 |
| Wong Mito Lab, |
RCV000851017 | SCV000993251 | benign | Juvenile myopathy, encephalopathy, lactic acidosis AND stroke | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.12153C>T variant in MT-TH gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 |
| Wong Mito Lab, |
RCV000851027 | SCV000993261 | benign | Juvenile myopathy, encephalopathy, lactic acidosis AND stroke | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.12175T>C variant in MT-TH gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 |
| Wong Mito Lab, |
RCV000851053 | SCV000993287 | benign | Juvenile myopathy, encephalopathy, lactic acidosis AND stroke | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.12236G>A variant in MT-TS2 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 |
| Equipe Genetique des Anomalies du Developpement, |
RCV000851176 | SCV000993410 | likely pathogenic | Marfanoid habitus and intellectual disability | criteria provided, single submitter | research | ||
| Gene |
RCV000984805 | SCV000998934 | likely pathogenic | not provided | 2018-02-26 | criteria provided, single submitter | clinical testing | The c.5419_5420insAlu variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is the result of an Alu mobile insertion element interrupting coding sequence in exon 30 and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Gene |
RCV001004047 | SCV000998935 | pathogenic | not provided | 2019-06-03 | criteria provided, single submitter | clinical testing | The c.1276_1277insAlu variant in the EFTUD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, we interpret c.1276_1277insAlu as a pathogenic variant. |
| Gene |
RCV000984894 | SCV000998936 | pathogenic | not provided | 2018-04-25 | criteria provided, single submitter | clinical testing | The c.426_427insAlu variant in the ETFB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This fetus harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 2000). Therefore, we interpret c.426_427insAlu as a pathogenic variant. |
| Gene |
RCV000984895 | SCV000998937 | pathogenic | not provided | 2019-06-21 | criteria provided, single submitter | clinical testing | Founder mutation in the Ashkenazi Jewish population which is observed in homozygous state in multiple unrelated patients in published literature (Tucker et al., 2011; Berzoykin et al., 2015), and not observed in homozygous state in controls. Mobile insertion element that consists of Alu sequence that is 353 base pairs in length, also described as c.1284_1285ins353 or c.428_429ins353 in the literature. Published functional studies demonstrate a damaging effect (loss of retina-specific isoform of MAK) (Tucker et al., 2011). Not observed in large population cohorts (Database of Genomic Variants). We interpret this as a Pathogenic Variant. |
| Gene |
RCV000984896 | SCV000998938 | pathogenic | not provided | 2018-02-01 | criteria provided, single submitter | clinical testing | The c.1926_1927insAlu variant in the NSD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 2000). Additionally, Alu-mediated recombination leading to microdeletions of the NSD1 gene has been previously described in individuals with Sotos syndrome (Mochizuki et al., 2008). Therefore, we interpret c.1926_1927insAlu as a pathogenic variant. |
| Gene |
RCV000985237 | SCV000999045 | pathogenic | not provided | 2018-06-12 | criteria provided, single submitter | clinical testing | The c.431_432insAlu variant in the OFD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, we interpret c.431_432insAlu as a pathogenic variant. |
| Gene |
RCV000985238 | SCV000999047 | likely pathogenic | not provided | 2018-12-10 | criteria provided, single submitter | clinical testing | The c.131+2_c.131+3insAlu variant in the SLC26A3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 2000). Therefore, we interpret c.131+2_c.131+3insAlu as a likely pathogenic variant. |
| Gene |
RCV000985239 | SCV000999048 | pathogenic | not provided | 2019-03-13 | criteria provided, single submitter | clinical testing | The c.8932_8933insAlu variant in the USH2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian, 1999). Therefore, we interpret c.8932_8933insAlu as a pathogenic variant. |
| Gene |
RCV000985240 | SCV000999049 | pathogenic | not provided | 2018-11-15 | criteria provided, single submitter | clinical testing | The c.1600_1601insAlu variant in the ZEB2 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is the result of an Alu mobile insertion element interrupting coding sequence in exon 8 and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, this variant is considered a pathogenic variant. |
| Gene |
RCV000985241 | SCV000999050 | pathogenic | not provided | 2019-08-22 | criteria provided, single submitter | clinical testing | Has not been previously reported as pathogenic or benign to our knowledge. Not observed in large population cohorts (MacDonald et al., 2014). This variant is the result of an Alu mobile insertion element interrupting coding sequence in exon 30 and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). We interpret this as a Pathogenic Variant. |
| Human Genome Sequencing Center Clinical Lab, |
RCV001171631 | SCV000999934 | pathogenic | Intellectual disability | 2019-11-18 | criteria provided, single submitter | research | The variant is a deletion overlapping coding exons of CRHR1, SPPL2C, MAPT, STH genes, and exons 3-15 of the KANSL1 gene. Deletions overlapping KANSL1 gene have been shown to cause Koolen-de Vries syndrome, a clinically heterogeneous disorder characterized by hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism (PMID: 22544363, 26306646). This variant was identified in an adult undergoing exome sequencing due to a history of intellectual disability and developmental delay. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001004047 | SCV001142746 | pathogenic | not provided | 2019-06-03 | criteria provided, single submitter | clinical testing | The c.1276_1277insAlu variant in the EFTUD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, we interpret c.1276_1277insAlu as a pathogenic variant. |
| Athena Diagnostics Inc | RCV000992385 | SCV001144614 | benign | not provided | 2018-11-19 | criteria provided, single submitter | clinical testing | |
| Cavalleri Lab, |
RCV001031017 | SCV001160792 | pathogenic | 16p11.2 deletion syndrome | 2019-12-11 | criteria provided, single submitter | research | |
| Broad Institute Rare Disease Group, |
RCV001005017 | SCV001164581 | likely pathogenic | Duchenne muscular dystrophy | 2018-12-03 | criteria provided, single submitter | research | The heteroygous deletion variant in DMD was identified by our study in one female with Duchenne Muscular Dystrophy. Manifesting female carriers of DMD have been previously reported (Mercieret al., 2013). This deletion variant in DMD has not been previously reported in individuals with Duchenne Muscular Dystrophy and was absent from large population studies. This variant is a deletion of Exon 1 and 2 and is predicted to impact the protein, including the start codon. Loss of function of the DMD gene is an established disease mechanism in autosomal recessive Duchenne Muscular Dystrophy. A splice site variant affecting Exon 2 has been reported pathogenic for Duchenne Muscular Dystrophy in ClinVar by Invitae and EGL Genetic Diagnostics, suggesting that Exon 2 is important for protein function (Variation ID: 283346). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. |
| NIHR Bioresource Rare Diseases, |
RCV001027727 | SCV001190163 | pathogenic | Common variable agammaglobulinemia | 2019-01-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV001027728 | SCV001190164 | pathogenic | Common variable agammaglobulinemia | 2019-01-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV001027643 | SCV001190215 | likely pathogenic | Inherited Immunodeficiency Diseases | 2019-01-01 | criteria provided, single submitter | research | |
| Central Laboratory, |
RCV001200047 | SCV001190325 | pathogenic | 22q13.3 interstitial deletion | 2020-03-09 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001089808 | SCV001245295 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-02-04 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.6003_6004insAlu), causing a frameshift at codon 2002 (p.Glu2002fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BRCA2-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089809 | SCV001245296 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-12-11 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.2844_2845insAlu), causing a frameshift at codon 948 (p.Val948fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BRCA2-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this allele has been classified as Pathogenic. |
| Invitae | RCV001089810 | SCV001245297 | likely pathogenic | Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J | 2019-06-06 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 326 of the TTN mRNA (c.85261_85262insAlu), causing a frameshift at codon 28421 (p.Ile28421fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this insertion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV001089811 | SCV001245298 | pathogenic | not provided | 2019-06-10 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 22 of the PHEX mRNA (c.2193_2194insAlu), causing a frameshift at codon 731 (p.Phe731fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acids of the PHEX protein. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the PHEX protein. Other variant(s) that disrupt this region (p.Arg747*) have been determined to be pathogenic (PMID: 9199930, 9768674). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089812 | SCV001245299 | pathogenic | Neurofibromatosis, type 1 | 2019-04-07 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 2 of the NF1 mRNA (c.195_196insAlu), causing a frameshift at codon 65 (p.Val65fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538) and other Alu-mediated insertions in NF1 have been reported to be de novo in the literature (PMID: 1719426). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089813 | SCV001245300 | pathogenic | Ataxia-telangiectasia syndrome | 2019-07-05 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 5 of the ATM gene (c.364_365delinsAlu), causing a frameshift at codon 122 (p.Asnfs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089815 | SCV001245302 | uncertain significance | Mitochondrial trifunctional protein deficiency; Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2019-09-05 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in intron 2 of the HADHA gene (c.110-25_110-24insAlu). It does not directly change the encoded amino acid sequence of the HADHA protein and it is unknown how it will affect the protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HADHA-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV001089816 | SCV001245303 | pathogenic | Neurofibromatosis, type 1 | 2019-05-03 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 32 of the NF1 gene (c.4320_4321insAlu), causing a frameshift at codon p.Met1440 (p.Met1440fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089817 | SCV001245304 | pathogenic | Familial cancer of breast | 2019-06-07 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 13 of the CHEK2 gene (c.1406_1407insAlu), causing a frameshift at codon 469 (p.Val469fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CHEK2-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089818 | SCV001245305 | pathogenic | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2019-12-22 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 6 of the CRB1 gene (c.1454_1455insAlu), causing a frameshift at codon 486 (p.Leu486fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CRB1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089819 | SCV001245306 | pathogenic | Ataxia-telangiectasia syndrome | 2019-12-15 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 19 of the ATM mRNA (c.2852_2853insAlu), causing a frameshift at codon 951 (p.Leu951fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089820 | SCV001245307 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-02-16 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 16 of the BRCA2 mRNA (c.7665_7666insAlu), causing a frameshift at codon 2556 (p.Asn2556fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584) and other Alu-mediated insertions in BRCA2 have been reported in the literature (PMID: 20232141). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089821 | SCV001245308 | pathogenic | Ataxia-telangiectasia syndrome | 2019-12-11 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 20 of the ATM gene (c.3055_3056insAlu), causing a frameshift at codon 1019 (p.Leu1019fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089822 | SCV001245309 | pathogenic | Familial hypocalciuric hypercalcemia; Hypocalcemia, autosomal dominant 1 | 2020-01-07 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 7 of the CASR mRNA (c.2643_2644insAlu), causing a frameshift at codon 882 (p.Lys882fs). While this insertion is not anticipated to result in nonsense mediated decay, it is expected to disrupt the C-terminus of the CASR protein. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). A similar Alu-mediated insertion in CASR have been reported to segregate with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) in three Nova Scotian families (PMID: 7717399, 9217223). Experimental studies have shown that a similar Alu-mediated insertion causes no response to Ca2+ and decreases cell surface expression of the CASR receptor protein in vitro (PMID: 9109436). This Alu-mediated insertion is expected to disrupt a portion of the C-terminal region of the CASR protein containing the intracellular domain (residues 862-1078) (PMID: 20374733). In addition, missense substitutions at codon 886 (p.Arg886Trp and p.Arg886Pro) have been reported in families affected with FHH and have been determined to be likely pathogenic (PMID: 17698911, 11807402, 20798521). This suggests that disruption of this region is causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089823 | SCV001245310 | pathogenic | PTEN hamartoma tumor syndrome | 2019-05-14 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 5 of the PTEN mRNA (c.432_433insAlu), causing a frameshift at codon 145 (p.Phe145fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675) and similar Alu-mediated insertions in PTEN have been reported in individuals affected with Cowden syndrome (PMID: 28513612). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089824 | SCV001245311 | pathogenic | Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma | 2019-12-15 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 3 of the SDHB gene (c.250_251insAlu), causing a frameshift at codon 84 (p.Asp84fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with SDHB-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089825 | SCV001245312 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.3083_3084insAlu), causing a frameshift at codon 1028 (p.Lys1028fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BRCA2-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089829 | SCV001245316 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 10 | 2019-01-17 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 10 of the POT1 gene (c.717_718insAlu), causing a frameshift at codon 240 (p.Arg240fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POT1-related conditions. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in POT1 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Invitae | RCV001089830 | SCV001245317 | pathogenic | not provided | 2019-02-11 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 33 of the VPS13A mRNA (c.3525_3526insAlu), causing a frameshift at codon 1176 (p.Gln1176fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VPS13A-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Loss-of-function variants in VPS13A are known to be pathogenic (PMID: 12404112, 21598378). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089831 | SCV001245318 | pathogenic | Angiokeratoma corporis diffusum | 2019-09-03 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 5 of the GLA mRNA (c.744_745insAlu), causing a frameshift at codon 249 (p.Asn249fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089832 | SCV001245319 | pathogenic | Cystic fibrosis | 2019-07-28 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 24 of the CFTR gene (c.3955_3956insAlu), causing a frameshift at codon 1319 (p.Ala1319fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089833 | SCV001245320 | pathogenic | Duchenne muscular dystrophy | 2019-09-09 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 43 of the DMD mRNA (c.6220_6221insAlu), causing a premature translational stop signal (p.Leu2074_Met3685delinsArgSerIleAsnPheValAspMetGlnPro*). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DMD-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089834 | SCV001245321 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-09-24 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.3082_3083insAlu), causing a frameshift at codon 1028 (p.Lys1028fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089835 | SCV001245322 | pathogenic | not provided | 2019-10-17 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the RP1 gene (c.4052_4053insAlu), causing a frameshift at codon 1352 (p.Tyr1352Alafs*9). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). A similar variant has been observed in individual(s) with autosomal recessive retinal disease (PMID: 30913292, 31253780). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. That variant is also known as c.4052_4053ins328 (p.Tyr1352Alafs*9) in the literature. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to disrupt protein function (PMID: 19763152, 20307669, 22406018). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089836 | SCV001245323 | pathogenic | Ataxia-telangiectasia syndrome | 2020-01-19 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 50 of the ATM gene (c.7388_7389insAlu), causing a frameshift at codon 2463 (p.Leu2463fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089839 | SCV001245326 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-08-30 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the PMS2 gene (c.1848_1849insAlu), causing a frameshift at codon 617 (p.Pro617fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089840 | SCV001245327 | pathogenic | Li-Fraumeni syndrome | 2019-06-30 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 9 of the TP53 gene (c.970_971insAlu), causing a frameshift at codon 324 (p.Asp324fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with TP53-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089842 | SCV001245329 | pathogenic | Alstrom syndrome | 2019-12-13 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 20 of the ALMS1 gene (c.12184_12185insAlu), causing a frameshift at codon 4062 (p.Leu4062fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALMS1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089843 | SCV001245330 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-11-04 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 12 of the MSH2 mRNA (c.1972_1973insAlu), causing a frameshift at codon 658 (p.Glu658fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089844 | SCV001245331 | pathogenic | Familial cancer of breast | 2019-12-19 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 9 of the CHEK2 gene (c.985_986insAlu), causing a frameshift at codon 329 (p.Tyr329fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CHEK2-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089845 | SCV001245332 | pathogenic | not provided | 2019-12-18 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 16 of the PHEX gene (c.1681_1682insAlu), causing a frameshift at codon 560 (p.Phe560fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PHEX-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089846 | SCV001245333 | pathogenic | not provided | 2020-01-03 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 9 of the MAK gene (c.1297_1298insAlu), causing a frameshift at codon 433 (p.Lys433fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. A similar Alu insertion has been observed in homozygosity in many individuals affected with autosomal recessive retinitis pigmentosa and may be a Jewish founder variant (PMID: 21825139, 25097241). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 21825139). Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in MAK are known to be pathogenic (PMID: 21148103, 21825139, 24938718, 29781741). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089847 | SCV001245334 | pathogenic | not provided | 2019-12-24 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the RP1 gene (c.2321_2322insAlu), causing a frameshift at codon 774 (p.Leu774fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1383 amino acids of the RP1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with autosomal dominant retinal disease (Invitae). This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089848 | SCV001245335 | pathogenic | Bardet-Biedl syndrome | 2019-03-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala406Glnfs*65) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BBS1-related conditions. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089849 | SCV001245336 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-10-07 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 10 of the BRCA1 gene (c.3950_3951insAlu), causing a frameshift at codon 1317 (p.Leu1317fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089850 | SCV001245337 | likely pathogenic | Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J | 2019-02-08 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 273 of the TTN mRNA (c.52063_52064insAlu), causing a frameshift at codon 17355. This creates a premature translational stop signal (p.His17355Argfs*17) and is expected to result in a disrupted protein product. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy and are considered to be likely pathogenic for the disease (PMID: 25589632). For these reasons, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV001089851 | SCV001245338 | pathogenic | Fanconi anemia | 2019-04-23 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 14 of the FANCM gene (c.4143_4144insAlu), causing a frameshift at codon 1382 (p.Asp1382fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Similar retrotransposon insertions have not been reported in the literature in individuals with FANCM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in FANCM are known to be pathogenic (PMID: 29895858, 30075111). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089852 | SCV001245339 | pathogenic | Multiple fibrofolliculomas | 2019-11-06 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 14 of the FLCN gene (c.1557_1558insAlu), causing a frameshift at codon 520 (p.Lys520fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 78 amino acids of the FLCN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLCN-related conditions. This variant disrupts the C-terminus of the FLCN protein. Other variant(s) that disrupt this region (p.Arg527*) have been determined to be pathogenic (PMID: 15852235, 17028174, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089853 | SCV001245340 | pathogenic | not provided | 2019-10-30 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the RP1 gene (c.3352_3353insAlu), causing a frameshift at codon 1117 (p.Phe1117fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RP1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089855 | SCV001245342 | pathogenic | Ataxia-telangiectasia syndrome | 2019-11-11 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 23 of the ATM gene (c.3292_3293insAlu), causing a frameshift at codon 1097 (p.Phe1097fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089856 | SCV001245343 | pathogenic | Hypertrophic cardiomyopathy | 2019-08-09 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 33 of the MYBPC3 mRNA (c.3659_3660insAlu), causing a frameshift at codon 1220 (p.Asp1220fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with MYBPC3-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089857 | SCV001245344 | pathogenic | Eichsfeld type congenital muscular dystrophy | 2019-05-10 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 4 of the SELENON mRNA (c.487_488insAlu), causing a frameshift at codon 163 (p.Gln163fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). While this particular variant has not been reported in the literature, loss of function variants in SELENON are known to be pathogenic (PMID: 21670436, 12192640). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001089858 | SCV001245345 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-07-07 | criteria provided, single submitter | clinical testing | This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.5007_5008insAlu), causing a frameshift at codon 1670 (p.Ala1670fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). A retrotransposon insertion at this location in BRCA2 has been reported in individuals undergoing testing for hereditary breast and ovarian cancer (PMID: 29025590) For these reasons, this variant has been classified as Pathogenic. |
| Genetics and Genomics, |
RCV001095544 | SCV001245472 | likely pathogenic | Hiatus hernia; Expressive language delay; Microcephaly; Delayed gross motor development; Mild short stature; Delayed fine motor development | 2020-05-04 | criteria provided, single submitter | clinical testing | This duplication was classified as likely pathogenic due to segregation studies and its absence from controls. |
| Undiagnosed Diseases Network, |
RCV001090143 | SCV001245589 | likely pathogenic | FAM177A1-related disorder | 2019-10-31 | criteria provided, single submitter | clinical testing | Observed in proband and similarly affected sister. |
| Undiagnosed Diseases Network, |
RCV001090215 | SCV001245610 | pathogenic | Developmental delay, intellectual disability, obesity, and dysmorphic features | 2019-09-20 | criteria provided, single submitter | clinical testing | |
| Broad Institute Rare Disease Group, |
RCV001171638 | SCV001250685 | uncertain significance | Global developmental delay; Short stature; Macrocephalus; Chorea | 2020-05-13 | criteria provided, single submitter | research | A heterozygous deletion of the full coding sequence of the RTN4IP1 gene has been identified by our study in an individual with infantile chorea, short stature, macrocephaly, and global developmental delay with regression. This variant was identified in the compound heterozygous state, along with a missense variant of uncertain significance. The break points of this deletion are located in the intronic regions of adjacent genes (5', QRSL; 3' CRYBG1). This variant has not been reported in the literature in any individuals with RTN4IP1-related disease. Loss of function of RTN4IP1 in an autosomal recessive disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, while a whole gene deletion in a recessive gene is suspicious for a pathogenic role, the clinical significance of the chr6:106539151-106629957 deletion is uncertain. (0 points, Riggs 2020). |
| Turner Lab, |
RCV001174506 | SCV001251650 | pathogenic | Chromosome 9p deletion syndrome | 2020-05-07 | criteria provided, single submitter | research | This individual contains a deletion on chromosome 9 (consistent with 9p- syndrome) and also a translocation of a portion of chromosome 13 onto the chromosome 9 with the deletion. The full variant in karyotype form is 46,XX,der(9)t(9;13)(p23;q13). |
| Neurogenetics Research Program, |
RCV001194626 | SCV001338856 | pathogenic | Allan-Herndon-Dudley syndrome | 2020-01-29 | criteria provided, single submitter | research | |
| Blueprint Genetics | RCV001250749 | SCV001426168 | pathogenic | Angelman syndrome | 2017-11-24 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001250750 | SCV001426169 | pathogenic | Angelman syndrome | 2018-06-19 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001250751 | SCV001426170 | pathogenic | Angelman syndrome | 2018-11-02 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001250752 | SCV001426171 | risk factor | 16p11.2 deletion syndrome | 2017-12-08 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001250753 | SCV001426172 | pathogenic | Mowat-Wilson syndrome | 2018-03-22 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001250754 | SCV001426173 | pathogenic | Chromosome 1p36 deletion syndrome | 2018-05-09 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics of Inherited Kidney Disorders Laboratory, |
RCV001254216 | SCV001430285 | pathogenic | Autosomal dominant polycystic kidney disease | 2019-01-01 | criteria provided, single submitter | research | |
| Molecular Genetics of Inherited Kidney Disorders Laboratory, |
RCV001254217 | SCV001430286 | pathogenic | Autosomal dominant polycystic kidney disease | 2019-01-01 | criteria provided, single submitter | research | |
| Molecular Genetics of Inherited Kidney Disorders Laboratory, |
RCV001254247 | SCV001430287 | pathogenic | Autosomal dominant polycystic kidney disease | 2019-01-01 | criteria provided, single submitter | research | |
| Molecular Genetics of Inherited Kidney Disorders Laboratory, |
RCV001256004 | SCV001430883 | pathogenic | Autosomal dominant polycystic kidney disease | 2019-01-01 | criteria provided, single submitter | research | |
| Undiagnosed Diseases Network, |
RCV001255606 | SCV001432132 | likely pathogenic | Intellectual disability, autosomal dominant 56 | 2020-04-01 | criteria provided, single submitter | clinical testing | This deletion was inherited from his father, who has a history of learning disabilities. |
| Undiagnosed Diseases Network, |
RCV001255610 | SCV001432136 | uncertain significance | Wolf-Hirschhorn like syndrome | 2020-05-07 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV001255967 | SCV001432743 | uncertain significance | ELFN1-related condition | 2018-09-18 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV001255970 | SCV001432747 | pathogenic | Epileptic encephalopathy, early infantile, 28 | 2020-07-08 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV001255971 | SCV001432748 | pathogenic | Wieacker-Wolff syndrome, female-restricted | 2020-05-26 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV001255972 | SCV001432749 | pathogenic | Koolen-de Vries syndrome | 2020-05-29 | criteria provided, single submitter | clinical testing | |
| Laboratory of Medical Genetics, |
RCV001257570 | SCV001433614 | likely pathogenic | Intellectual disability, autosomal dominant 57 | 2020-09-24 | criteria provided, single submitter | research | The deletion spans TLK2 and has been identified in a proband with intellectual disability and delayed motor development. The variant was de novo. The cells carrying the deletion show chromatin relaxation. |
| INGEBI, |
RCV001257507 | SCV001434335 | pathogenic | Nonsyndromic hearing loss and deafness | 2020-08-31 | criteria provided, single submitter | clinical testing | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the deletion (g.20797177_21105945del) known as del(GJB6-D13S1830) eliminates a 309-kb fragment including the first five exons (and a portion of the sixth exon) of GJB6 and the whole CRYL1 genes. It was demonstrated that CX26 and Cx30 can form heteromeric connexons and heterotypic gap-junction channels (PMID: 14681039). The GJB2+/- GJB6+/tm1Kwi double heterozygous mice have moderate hearing loss and a significantly reduced of endocochlear potential (PMID: 12917317, 28823936). In addition to this, functional studies in mice demonstrated that the GJB6tm1Kwi mouse is not only a GJB6 knockout but also decreases the transcription of the contiguous GJB2 gene (PMID: 19047647, 22098503). Furthermore, an independent GJB6 knock-out strain that carries a complete deletion of the GJB6 coding sequence, without inserted material, diminish the effect on GJB2 decrease expression (PMID:23303923 ). Therefore, this evidence supports the existence of a regulatory element within some part of the deletion among with the digenic pattern mode of inheritance proposed (PS3). The filter allele frequency of this variant is 0.02% from Genome Aggregation Database and Database of Genomic Variants (last update 01-04-2020 and 17-05-2020 respectively) meeting PM2_Supporting criteria. This variant was found to have a statistically higher prevalence in affected individuals over controls (PS4; PMID: 11807148). The del(GJB6-D13S1830) variant has been detected in trans with at least 4 GJB2 pathogenic variants applying to PM3_VeryStrong rule (PMID: 24158611, 11807148, 14571368). Therefore, this variant meets criteria to be classified as pathogenic for autosomal recessive non-syndromic hearing loss (PS3, PS4, PM2_Supporting, PM3_VeryStrong). |
| INGEBI, |
RCV001257508 | SCV001434336 | pathogenic | Nonsyndromic hearing loss and deafness | 2020-08-31 | criteria provided, single submitter | clinical testing | The deletion: del(GJB6-D13S1854) (g.20802727_21034768del) eliminates a 232-kb fragment including the first five exons of GJB6 and the last 4 exons of CRYL1 gene. It was demonstrated that CX26 and Cx30 can form heteromeric connexons and heterotypic gap-junction channels (PMID: 14681039). Besides, Gjb2+/- Gjb6+/tm1Kwi double heterozygous mice have moderate hearing loss and a significantly reduced endocochlear potential (PMID: 12917317, 28823936) In addition to this, functional studies in mice demonstrated that the Gjb6tm1Kwi mouse is not only a Gjb6 knockout but also decreases the transcription of the contiguous Gjb2 gene (PMID:19047647, 22098503). Furthermore, an independent Gjb6 knock-out strain that carries a complete deletion of the Gjb6 coding sequence, without inserted material, diminish the effect on GJB2 decrease expression (PMID:23303923 ). Therefore, these evidence support the existence of the regulatory element within some part of the deletion among with the digenic pattern mode of inheritance proposed. (PS3). This deletion is absent from Genome Aggregation Database and Database meeting PM2 rule. This variant was found to have a statistically higher prevalence in affected individuals over controls (PS4; PMID: 11807148). The del(GJB6-D13S1854) variant has been detected in trans with at least 4 pathogenic variants in GJB2 in hearing loss patients applying to PM3_VeryStrong rule (PMID: 15994881, 24158611). Therefore, this variant meets criteria to be classified as pathogenic for autosomal recessive non-syndromic hearing loss (PS3, PS4, PM3_S, PM2). |
| Rady Children's Institute for Genomic Medicine, |
RCV001260502 | SCV001437523 | uncertain significance | not provided | 2019-11-05 | criteria provided, single submitter | clinical testing | A deletion of approximately 1235.340 KB (chr14:22006109-23241448x1) located at 14q11.2 and encompassing 127 genes was detected in this individual. Deletions involving 14q11.2 have been previously reported in individuals with autism, developmental delay, intellectual disability, and seizures in DECIPHER. However, deletions involving 14q11.2 have also been observed in the Database of Genomic Variants and classified as benign in ClinVar. Based on the available evidence, this deletion is classified as a Variant of Uncertain Significance. |
| Rady Children's Institute for Genomic Medicine, |
RCV001260503 | SCV001437524 | pathogenic | not provided | 2020-05-13 | criteria provided, single submitter | clinical testing | A deletion of approximately 7.5 Mb (chr10:81585301-89101700x1) located at 10q22.3q23.2 was detected in this individual. This deletion encompasses 31 protein encoding genes of which 7 have been reported in OMIM with a disease-association (PMID: 19344873). Pathogenic deletions involving this region are associated with Chromosome 10q22.3-q23.2 deletion syndrome (MIM: #612242), and have been previously reported in patients with dysmorphic features, developmental delay, behavioral concerns, limb anomalies, and congenital heart defects (PMID: 28588438, 21248748, 20345475). The reported congenital heart defects are of variable severity and include: patent ductus arteriosus, atrioventricular septal defect, tetralogy of Fallot, pulmonic regurgitation, tricuspid regurgitation, and ventricular septal defect (PMID: 28588438). This variant has not been observed at a significant frequency in the Database of Genomic Variants and thus is presumed to be rare. This result was confirmed by orthogonal testing. Analysis of the parental samples showed that the mother is negative and the father is negative for this variant, indicating that the 7.5 Mb deletion likely occurred as a de novo event in the proband. Based on the available evidence, this deletion is classified as Pathogenic. |
| Rady Children's Institute for Genomic Medicine, |
RCV001260932 | SCV001438021 | pathogenic | not provided | 2019-09-16 | criteria provided, single submitter | clinical testing | A 12.9 MB deletion on chromosome 13 (chr13:102175801-115169858del) encompassing the CARKD gene was identified in this patient, in trans with a missense variant in CARKD c.1112C>T (p.Ser371Leu) that was classified as Likely Pathogenic. On the basis of this evidence, the 12.9 MB deletion was classified as Pathogenic. |
| NIHR Bioresource Rare Diseases, |
RCV001262039 | SCV001439417 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2018-01-01 | criteria provided, single submitter | research | PVS1+PM2+PP4 |
| NIHR Bioresource Rare Diseases, |
RCV001262041 | SCV001439419 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2018-01-01 | criteria provided, single submitter | research | PVS1+PM2+PP4 |
| NIHR Bioresource Rare Diseases, |
RCV001262047 | SCV001439425 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2018-01-01 | criteria provided, single submitter | research | PVS1+PM2+PP4 |
| Center for Statistical Genetics, |
RCV001261860 | SCV001448212 | pathogenic | Intellectual disability | 2020-10-16 | criteria provided, single submitter | research | |
| Bertuch Lab, |
RCV001523792 | SCV001450739 | pathogenic | Chromosome 16q22 deletion syndrome | criteria provided, single submitter | clinical testing | This structural variant results in whole gene deletion of CARMIL2, ACD, PARD6A, ENKD1, C16orf86, and GFOD2, as well as partial deletion of CTCF and RANBP10. When heterozygous, this chromosomal deletion resulted in chr16q22.1 microdeletion syndrome, with phenotypes of developmental delay, poor growth, facial dysmorphism, and hypotonia. Telomere lengths were found to be between the 1st and 10th centiles for age in the five lymphocyte populations, although similar to the lengths of the proband's parents who did not have the chromosomal deletion. Multiple CBCs obtained between the ages of 16 months and 4 years were normal. | |
| Dept. |
RCV001376650 | SCV001450780 | likely benign | Developmental cataract | 2020-12-01 | criteria provided, single submitter | research | |
| Dept. |
RCV001376651 | SCV001450781 | likely benign | Developmental cataract | 2020-12-01 | criteria provided, single submitter | research | |
| Institute of Medical Molecular Genetics, |
RCV001270921 | SCV001451705 | pathogenic | Congenital miosis | 2020-12-21 | criteria provided, single submitter | clinical testing | |
| Center for Statistical Genetics, |
RCV001271073 | SCV001451899 | uncertain significance | Intellectual disability | 2020-10-02 | criteria provided, single submitter | clinical testing | |
| MNM Diagnostics | RCV001271109 | SCV001451953 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2019-09-05 | criteria provided, single submitter | clinical testing | The variant fulfills the pathogenic criteria due to the following observations. This is a truncating mutation that deletes 6 final exons of the gene, whose loss of function is responsible for disease onset (PVS1). The funcional protein domain is deleted (PM1). Patient's phenotype is specific for a disease with monogenic etiology (PP4), namely hipophosphatemic rickets (XLHR). |
| Hadassah Hebrew University Medical Center | RCV001293248 | SCV001468314 | pathogenic | Harel-Yoon syndrome | criteria provided, single submitter | clinical testing | ||
| Hadassah Hebrew University Medical Center | RCV001293249 | SCV001468315 | pathogenic | Harel-Yoon syndrome | criteria provided, single submitter | clinical testing | ||
| Hadassah Hebrew University Medical Center | RCV001293250 | SCV001468316 | pathogenic | Harel-Yoon syndrome | criteria provided, single submitter | clinical testing | ||
| Hadassah Hebrew University Medical Center | RCV001293251 | SCV001468317 | pathogenic | Harel-Yoon syndrome | criteria provided, single submitter | clinical testing | ||
| New York Genome Center | RCV001281486 | SCV001468794 | uncertain significance | Seizures | 2019-09-04 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001281541 | SCV001468850 | uncertain significance | Heart, malformation of; Intellectual disability | 2019-07-17 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001291765 | SCV001480382 | uncertain significance | See cases | 2020-05-26 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001291766 | SCV001480383 | uncertain significance | See cases | 2020-05-26 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001291781 | SCV001480399 | uncertain significance | See cases | 2020-04-20 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV001310223 | SCV001499834 | pathogenic | Immunodeficiency 67 | 2020-11-25 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001311773 | SCV001502074 | uncertain significance | not provided | 2020-08-01 | criteria provided, single submitter | clinical testing | |
| MNM Diagnostics | RCV001312195 | SCV001502657 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2020-01-24 | criteria provided, single submitter | clinical testing | This is a hemizygotic deletion spanning two last exons (21-22) of PHEX gene and CBLL2 gene. LOF mutations in PHEX gene are responsible for the X-linked hypophosphatemic rickets (XLHD). Deletion of two last exons were described previously in relation to a XLHD patient (PMID: 19513579). The variant was previously identified as pathogenic (HGMD: CG097917). |
| The Molecular Genetic Diagnosis Center, |
RCV001352677 | SCV001519656 | likely pathogenic | Inflammatory bowel disease 28, autosomal recessive | 2021-01-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001352683 | SCV001547262 | uncertain significance | not provided | 2020-05-20 | criteria provided, single submitter | clinical testing | Describes a nucleotide substitution 898 basepairs upstream of the ATG translational start site in the PTEN promoter region; Variants within the PTEN promoter have been observed in individuals with features of Cowden syndrome (Zhou 2003); Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant; Also known as c.-897C>T |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001578513 | SCV001547742 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | Absent from gnomAD v2.1.1 (PM2_moderate) |
| Genetics and Prenatal Diagnosis Center, |
RCV001391666 | SCV001593290 | pathogenic | Syndromic X-linked intellectual disability Lubs type | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391667 | SCV001593291 | pathogenic | Deletion of short arm of chromosome 18 | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391668 | SCV001593292 | pathogenic | Developmental delay with variable intellectual impairment and behavioral abnormalities | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391669 | SCV001593293 | pathogenic | not provided | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391670 | SCV001593294 | pathogenic | Chromosome 10q26 deletion syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391671 | SCV001593295 | pathogenic | 16p11.2 deletion syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391672 | SCV001593296 | pathogenic | DiGeorge Syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391673 | SCV001593297 | pathogenic | Sudanophilic leukodystrophy; Hereditary spastic paraplegia 2 | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391674 | SCV001593298 | likely pathogenic | Chromosome 15q26-qter deletion syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391675 | SCV001593299 | pathogenic | DiGeorge Syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391676 | SCV001593300 | likely pathogenic | 16p11.2 deletion syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391677 | SCV001593301 | pathogenic | Anal atresia, hypospadias, and penoscrotal inversion | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Genetics and Prenatal Diagnosis Center, |
RCV001391678 | SCV001593302 | likely pathogenic | not provided | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001420574 | SCV001622889 | uncertain significance | See cases | 2020-05-07 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001420594 | SCV001622911 | likely pathogenic | Pitt-Hopkins-like syndrome 2 | 2020-05-19 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001420608 | SCV001622925 | uncertain significance | See cases | 2020-07-09 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001420629 | SCV001622953 | pathogenic | Chromosome 15q11-q13 duplication syndrome | 2020-06-05 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001420642 | SCV001622968 | uncertain significance | Febrile seizures, familial, 4 | 2020-05-19 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001420673 | SCV001623006 | uncertain significance | not provided | 2020-06-03 | criteria provided, single submitter | clinical testing | |
| Genetic Disease Research Branch / Genetics Development and Disease Section, |
RCV001420680 | SCV001623011 | pathogenic | Tyrosinase-positive oculocutaneous albinism | 2021-02-01 | criteria provided, single submitter | research | This represents a loss of function allele in OCA2 in a well described reccessive disease. ACMG: PVS1. PM4, PM3 |
| Genetic Disease Research Branch / Genetics Development and Disease Section, |
RCV001420681 | SCV001623012 | pathogenic | Tyrosinase-positive oculocutaneous albinism | 2021-02-01 | criteria provided, single submitter | research | |
| Mayo Clinic Laboratories, |
RCV001449852 | SCV001653249 | pathogenic | Familial hypercholesterolemia 1 | 2019-04-25 | criteria provided, single submitter | clinical testing | An in-frame duplication involving exons 2-6 of the LDLR gene. |
| Mayo Clinic Laboratories, |
RCV001449853 | SCV001653250 | pathogenic | not provided | 2020-09-24 | criteria provided, single submitter | clinical testing | An in-frame deletion involving exons 3-4 of the LDLR gene. |
| Mayo Clinic Laboratories, |
RCV001449854 | SCV001653251 | pathogenic | Familial hypercholesterolemia 1 | 2020-12-09 | criteria provided, single submitter | clinical testing | An in-frame deletion involving exons 3-5 of the LDLR gene. |
| Mayo Clinic Laboratories, |
RCV001449855 | SCV001653252 | pathogenic | Familial hypercholesterolemia 1 | 2019-09-18 | criteria provided, single submitter | clinical testing | An in-frame deletion of exon 5 of the LDLR gene. Exon 5 of LDLR encodes LR6, one of the LDLR class A repeats/ligand binding domains. PS3, PS4, PM1, PM3, PM4 |
| Mayo Clinic Laboratories, |
RCV001449856 | SCV001653253 | pathogenic | Familial hypercholesterolemia 1 | 2019-08-30 | criteria provided, single submitter | clinical testing | An out-of-frame deletion of exons 7-12 of the LDLR gene. PVS1, PM1, PM2 |
| Mayo Clinic Laboratories, |
RCV001449857 | SCV001653254 | pathogenic | Familial hypercholesterolemia 1 | 2019-11-21 | criteria provided, single submitter | clinical testing | An in-frame deletion of exon 15 of the LDLR gene. PS4, PP1_Strong, PS3_Moderate, PM2, PM4 |
| Mayo Clinic Laboratories, |
RCV001449858 | SCV001653255 | uncertain significance | not provided | 2019-06-14 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449859 | SCV001653256 | uncertain significance | not provided | 2021-03-24 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449860 | SCV001653257 | pathogenic | Marfan syndrome | 2020-04-23 | criteria provided, single submitter | clinical testing | An in-frame deletion of exons 43-46 of the FBN1 gene. PVS1_Strong, PS3, PP4 |
| Mayo Clinic Laboratories, |
RCV001449861 | SCV001653258 | pathogenic | not provided | 2020-10-07 | criteria provided, single submitter | clinical testing | A deletion of exons 30-35 of the MYBPC3 gene. PVS1, PM1, PM2 |
| Mayo Clinic Laboratories, |
RCV001449862 | SCV001653259 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2019-05-09 | criteria provided, single submitter | clinical testing | An out-of-frame duplication of exon 2 of the ENG gene. |
| Mayo Clinic Laboratories, |
RCV001449863 | SCV001653260 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2021-03-11 | criteria provided, single submitter | clinical testing | An out-of-frame deletion of exon 2 of the ENG gene. PVS1, PS4_moderate, PM2_supporting |
| Mayo Clinic Laboratories, |
RCV001449864 | SCV001653261 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2019-06-25 | criteria provided, single submitter | clinical testing | An in-frame deletion of exons 9-10 of the ENG gene. |
| Mayo Clinic Laboratories, |
RCV001449865 | SCV001653262 | pathogenic | Hereditary hemorrhagic telangiectasia type 1 | 2020-05-15 | criteria provided, single submitter | clinical testing | An in-frame deletion of exons 9-11 of the ENG gene. PVS1_Strong, PS4_moderate, PP5, PP4 |
| Mayo Clinic Laboratories, |
RCV001449866 | SCV001653263 | pathogenic | not provided | 2020-07-30 | criteria provided, single submitter | clinical testing | A whole gene deletion of the SLC2A1 gene. PVS1, PM2, PP4 |
| Mayo Clinic Laboratories, |
RCV001449867 | SCV001653264 | uncertain significance | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449868 | SCV001653265 | likely pathogenic | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | An out-of-frame deletion involving exon 2 of the NPRL3 gene. PVS1, PM2 |
| Mayo Clinic Laboratories, |
RCV001449869 | SCV001653266 | uncertain significance | not provided | 2020-04-22 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449870 | SCV001653267 | uncertain significance | not provided | 2021-01-05 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449871 | SCV001653268 | uncertain significance | not provided | 2021-01-05 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449872 | SCV001653269 | uncertain significance | not provided | 2020-10-15 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449873 | SCV001653270 | pathogenic | not provided | 2021-02-14 | criteria provided, single submitter | clinical testing | A whole gene deletion of the TSC2 gene. PVS1, PS4_moderate, PM2 |
| Mayo Clinic Laboratories, |
RCV001449874 | SCV001653271 | pathogenic | not provided | 2019-06-18 | criteria provided, single submitter | clinical testing | An out-of-frame deletion involving exons 8-9 of the CLN3 gene. PVS1, PS3, PS4, PM3 |
| Mayo Clinic Laboratories, |
RCV001449875 | SCV001653272 | pathogenic | not provided | 2020-01-29 | criteria provided, single submitter | clinical testing | A whole gene duplication of the PMP22 gene. |
| Mayo Clinic Laboratories, |
RCV001449876 | SCV001653273 | pathogenic | not provided | 2021-04-29 | criteria provided, single submitter | clinical testing | A whole gene deletion of the PMP22 gene. |
| Mayo Clinic Laboratories, |
RCV001449877 | SCV001653274 | likely pathogenic | not provided | 2019-12-25 | criteria provided, single submitter | clinical testing | A deletion involving exons 8-24 of the MAN2B1 gene. |
| Mayo Clinic Laboratories, |
RCV001449878 | SCV001653275 | uncertain significance | not provided | 2020-04-30 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001449879 | SCV001653276 | pathogenic | not provided | 2019-12-26 | criteria provided, single submitter | clinical testing | An out-of-frame duplication involving exons 61-62 of the DMD gene. |
| Mayo Clinic Laboratories, |
RCV001449880 | SCV001653277 | pathogenic | not provided | 2019-07-23 | criteria provided, single submitter | clinical testing | An in-frame deletion involving exons 45-57 of the DMD gene. |
| Mayo Clinic Laboratories, |
RCV001449881 | SCV001653278 | pathogenic | not provided | 2019-06-06 | criteria provided, single submitter | clinical testing | An out-of-frame deletion involving exon 45 of the DMD gene. |
| Neurogenetics Research Program, |
RCV001796573 | SCV001737583 | pathogenic | Cerebral palsy | 2021-06-10 | criteria provided, single submitter | research | Clinical diagnosis neurofibromatosis type 1. Cardiovascular complications are a feature of NF1. |
| Neurogenetics Research Program, |
RCV001796575 | SCV001737585 | pathogenic | Cerebral palsy | 2021-06-10 | criteria provided, single submitter | research | |
| Gene |
RCV001527755 | SCV001738886 | benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527805 | SCV001738942 | likely benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527809 | SCV001738946 | likely benign | not provided | 2020-01-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527827 | SCV001738965 | benign | not provided | 2019-04-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527829 | SCV001738967 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527873 | SCV001739016 | benign | not provided | 2019-09-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527882 | SCV001739025 | benign | not provided | 2019-05-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001527963 | SCV001739114 | benign | not provided | 2018-11-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001528058 | SCV001739219 | likely benign | not provided | 2019-05-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001528065 | SCV001739227 | benign | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530544 | SCV001745417 | benign | not provided | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530565 | SCV001745442 | benign | not provided | 2021-05-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530581 | SCV001745459 | benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530609 | SCV001745492 | likely benign | not provided | 2020-05-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530620 | SCV001745504 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530625 | SCV001745511 | likely benign | not provided | 2019-01-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530740 | SCV001745637 | likely benign | not provided | 2019-09-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530795 | SCV001745693 | benign | not provided | 2018-07-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530806 | SCV001745706 | benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001530920 | SCV001745832 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001531296 | SCV001746326 | likely benign | not provided | 2021-05-01 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001531653 | SCV001746886 | uncertain significance | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001531665 | SCV001746904 | likely benign | not provided | 2021-05-01 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001532159 | SCV001747588 | uncertain significance | not provided | 2021-05-01 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001532567 | SCV001748187 | likely benign | not provided | 2021-03-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001533796 | SCV001750657 | benign | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001533980 | SCV001750863 | benign | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001533993 | SCV001750878 | benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534023 | SCV001750911 | likely benign | not provided | 2018-07-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534169 | SCV001751072 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534191 | SCV001751095 | benign | not provided | 2019-01-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534262 | SCV001751173 | benign | not provided | 2021-05-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534283 | SCV001751199 | likely benign | not provided | 2019-08-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534295 | SCV001751212 | benign | not provided | 2018-11-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534319 | SCV001751239 | benign | not provided | 2019-02-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534360 | SCV001751283 | benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534429 | SCV001751358 | benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534530 | SCV001751470 | benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534549 | SCV001751490 | benign | not provided | 2021-05-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534569 | SCV001751512 | likely benign | not provided | 2018-09-07 | criteria provided, single submitter | clinical testing | |
| Kosik Lab, |
RCV001810749 | SCV001751549 | pathogenic | Alzheimer disease | 2021-07-01 | criteria provided, single submitter | case-control | |
| Gene |
RCV001534647 | SCV001751580 | likely benign | not provided | 2019-01-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534696 | SCV001751638 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534700 | SCV001751642 | benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534728 | SCV001751671 | benign | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534737 | SCV001751680 | likely benign | not provided | 2019-08-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534794 | SCV001751756 | likely benign | not provided | 2019-04-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534905 | SCV001751873 | benign | not provided | 2019-10-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534935 | SCV001751905 | benign | not provided | 2018-11-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534943 | SCV001751913 | benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535046 | SCV001752024 | likely benign | not provided | 2019-10-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535119 | SCV001752106 | benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535123 | SCV001752110 | likely benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535151 | SCV001752141 | benign | not provided | 2020-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535157 | SCV001752147 | benign | not provided | 2018-07-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535237 | SCV001752232 | benign | not provided | 2019-01-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535241 | SCV001752238 | benign | not provided | 2019-08-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535255 | SCV001752253 | likely benign | not provided | 2019-08-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535272 | SCV001752270 | likely benign | not provided | 2019-03-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001535300 | SCV001752304 | benign | not provided | 2021-05-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536184 | SCV001752906 | benign | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536186 | SCV001752908 | benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536239 | SCV001752968 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536371 | SCV001753121 | benign | not provided | 2021-05-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536394 | SCV001753145 | benign | not provided | 2019-11-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536480 | SCV001753244 | benign | not provided | 2021-05-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536553 | SCV001753328 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536556 | SCV001753331 | benign | not provided | 2018-07-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536567 | SCV001753345 | benign | not provided | 2018-12-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536600 | SCV001753380 | benign | not provided | 2019-09-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536606 | SCV001753386 | benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536681 | SCV001753476 | benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536719 | SCV001753521 | benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536726 | SCV001753529 | benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536784 | SCV001753592 | benign | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536823 | SCV001753633 | benign | not provided | 2018-12-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536829 | SCV001753639 | benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536870 | SCV001753681 | likely benign | not provided | 2020-05-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536875 | SCV001753687 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536881 | SCV001753695 | benign | not provided | 2018-10-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536936 | SCV001753752 | benign | not provided | 2018-09-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536937 | SCV001753754 | benign | not provided | 2018-07-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001536995 | SCV001753817 | benign | not provided | 2021-05-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537041 | SCV001753867 | benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537123 | SCV001753957 | benign | not provided | 2019-01-09 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 29588580) |
| Gene |
RCV001537142 | SCV001753983 | benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537207 | SCV001754061 | benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537211 | SCV001754065 | benign | not provided | 2019-08-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537287 | SCV001754152 | benign | not provided | 2018-08-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537296 | SCV001754162 | benign | not provided | 2018-07-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537309 | SCV001754178 | benign | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537402 | SCV001754281 | likely benign | not provided | 2018-10-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537408 | SCV001754291 | benign | not provided | 2021-06-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537427 | SCV001754311 | benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537456 | SCV001754341 | benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537480 | SCV001754367 | benign | not provided | 2021-05-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537499 | SCV001754386 | benign | not provided | 2019-08-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537513 | SCV001754400 | benign | not provided | 2019-11-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537590 | SCV001754489 | likely benign | not provided | 2019-11-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537619 | SCV001754518 | benign | not provided | 2019-02-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537625 | SCV001754526 | benign | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001537626 | SCV001754527 | likely benign | not provided | 2019-08-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538087 | SCV001755693 | benign | not provided | 2018-06-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538119 | SCV001755727 | likely benign | not provided | 2018-08-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538189 | SCV001755803 | likely benign | not provided | 2019-10-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538205 | SCV001755820 | benign | not provided | 2021-06-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538236 | SCV001755858 | benign | not provided | 2018-07-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538270 | SCV001755897 | benign | not provided | 2021-05-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538271 | SCV001755898 | benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538320 | SCV001755953 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538344 | SCV001755983 | likely benign | not provided | 2018-10-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538355 | SCV001755994 | benign | not provided | 2018-09-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538394 | SCV001756040 | benign | not provided | 2021-05-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538499 | SCV001756159 | likely benign | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538504 | SCV001756167 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538520 | SCV001756184 | benign | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538595 | SCV001756269 | benign | not provided | 2018-08-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538630 | SCV001756308 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538688 | SCV001756370 | benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538722 | SCV001756407 | benign | not provided | 2021-06-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538745 | SCV001756436 | benign | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538881 | SCV001756596 | benign | not provided | 2018-07-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538917 | SCV001756636 | benign | not provided | 2018-12-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538923 | SCV001756642 | benign | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538963 | SCV001756685 | benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001538978 | SCV001756701 | benign | not provided | 2018-08-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539000 | SCV001756727 | benign | not provided | 2019-03-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539002 | SCV001756729 | likely benign | not provided | 2018-07-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539044 | SCV001756776 | benign | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539047 | SCV001756779 | benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539082 | SCV001756819 | benign | not provided | 2020-08-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539134 | SCV001756878 | benign | not provided | 2021-05-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539181 | SCV001756925 | likely benign | not provided | 2018-07-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539239 | SCV001756986 | benign | not provided | 2018-06-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539328 | SCV001757087 | benign | not provided | 2020-12-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539340 | SCV001757102 | benign | not provided | 2019-06-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539382 | SCV001757152 | benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539398 | SCV001757172 | benign | not provided | 2018-07-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539443 | SCV001757225 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539489 | SCV001757275 | benign | not provided | 2019-08-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539490 | SCV001757276 | benign | not provided | 2021-06-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539506 | SCV001757293 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539591 | SCV001757379 | benign | not provided | 2019-08-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539692 | SCV001757492 | benign | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539716 | SCV001757519 | likely benign | not provided | 2019-01-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539837 | SCV001757656 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539896 | SCV001757720 | benign | not provided | 2021-04-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539918 | SCV001757743 | benign | not provided | 2021-05-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539951 | SCV001757779 | benign | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539988 | SCV001757818 | benign | not provided | 2018-07-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540039 | SCV001757875 | likely benign | not provided | 2019-01-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540129 | SCV001757975 | benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540155 | SCV001758007 | benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540181 | SCV001758036 | benign | not provided | 2018-10-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540294 | SCV001758166 | benign | not provided | 2018-07-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540477 | SCV001758368 | benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540538 | SCV001758432 | benign | not provided | 2021-06-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540549 | SCV001758444 | likely benign | not provided | 2018-09-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540617 | SCV001758519 | benign | not provided | 2018-06-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540772 | SCV001758693 | benign | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540860 | SCV001758788 | benign | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541076 | SCV001759031 | likely benign | not provided | 2019-06-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541088 | SCV001759043 | benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541090 | SCV001759046 | benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541203 | SCV001759172 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541222 | SCV001759194 | benign | not provided | 2021-05-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541328 | SCV001759308 | benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541387 | SCV001759380 | likely benign | not provided | 2018-11-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541412 | SCV001759409 | benign | not provided | 2018-08-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541551 | SCV001759565 | likely benign | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541563 | SCV001759580 | likely benign | not provided | 2019-08-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541604 | SCV001759623 | benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541634 | SCV001759656 | benign | not provided | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541652 | SCV001759677 | benign | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541671 | SCV001759697 | benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541697 | SCV001759725 | benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541849 | SCV001759888 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541855 | SCV001759896 | likely benign | not provided | 2020-03-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541875 | SCV001759921 | benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001541888 | SCV001759955 | benign | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
| Molecular Pathology Research Laboratory, |
RCV001541921 | SCV001760553 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| Molecular Pathology Research Laboratory, |
RCV001541922 | SCV001760554 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| Molecular Pathology Research Laboratory, |
RCV001541924 | SCV001760556 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| Molecular Pathology Research Laboratory, |
RCV001541925 | SCV001760557 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| Molecular Pathology Research Laboratory, |
RCV001541926 | SCV001760558 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| Molecular Pathology Research Laboratory, |
RCV001541927 | SCV001760559 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| Molecular Pathology Research Laboratory, |
RCV001541928 | SCV001760560 | pathogenic | Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PVS1, PS4_Supporting, PM2 |
| New York Genome Center | RCV001542276 | SCV001760959 | uncertain significance | not provided | 2020-06-12 | criteria provided, single submitter | clinical testing | The maternally inherited Xq21.1 duplication is a 323KB tandem duplication on the long arm of the X chromosome. This duplication contains 4 OMIM associated genes including full duplication of TAF9B and PGK1, as well as partial duplication of genes CYSLTR1 and ATP7A. To our current knowledge, the duplication identified in this individual has not been reported in the literature. Of the four OMIM associated genes within this duplication, two are disease associated. Pathogenic variants in PGK1 are associated with Phosphoglycerate kinase 1 deficiency (MIM#300653), and pathogenic variants in ATP7A are associated with Menkes disease (MIM#309400), Occipital horn syndrome (MIM#304150), and Spinal muscular atrophy, distal, X-Linked 3 (MIM#300489). Given the uncertainty regarding the functional consequence of the Xq21.1 duplication, it is reported here as a Variant of Uncertain Significance. |
| New York Genome Center | RCV001542282 | SCV001760965 | uncertain significance | not provided | 2020-05-29 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001542285 | SCV001760968 | uncertain significance | not provided | 2020-07-10 | criteria provided, single submitter | clinical testing | The inherited ~103 kb duplication identified overlaps with the well-known 1.4Mb recurrent 17q12 duplication [chr17:36,459,259-37,832,872, GRCh38, Reference 3]. The recurrent 1.4 Mb duplication contains 16 genes, four of which are located within the 103 kb duplication identified in this individual (ZNHIT3, MYO19, PIGW, and GGNBP2). Gene(s) responsible for clinical symptoms of the recurrent 1.4Mb 17q12 duplication are not identified yet [PMID: 26925472]. A 114 kb duplication involving full duplication of ZNHIT3, MYO19, and PIGW, as well as partial duplication of GGNBP2, TBC1D3G, and TBC1D3H is observed 117 times (55 homozygotes) in gnomAD SVs(v2.1). Given the uncertainty regarding the potential pathogenicity of ~103 kb duplication it is reported as a Variant of Uncertain Significance. |
| New York Genome Center | RCV001542300 | SCV001760985 | uncertain significance | not provided | 2020-07-03 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001542301 | SCV001760986 | uncertain significance | not provided | 2020-07-03 | criteria provided, single submitter | clinical testing | The inherited 16p11.2 duplication identified in this individual is a 223.3KB duplication on the short arm of chromosome 16. Chromosome 16p contains several low copy repeat sequences, called BP1-BP5, and non-homologous recombination between these sequences leads to syndromes associated with recurrent copy number gains and losses. The common, recurrent 16p11.2 duplication syndrome is a ~550KB recurrent copy number gain between BP4-BP5 [MIM#614671] [PMID:18184952; PMID:26629640]. The duplication identified here is an atypical distal duplication of 16p between BP2 and BP3, and contains OMIM associated genes ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, and LAT. Four of these genes are associated with autosomal recessive phenotypes including TUFM (AR Combined oxidative phosphorylation deficiency 4; MIM#610678), ATP2A1 (AR Brody Myopathy; MIM#601003), CD19 (AR Immunodeficiency, common variable 3;MIM#613493), and LAT (AR Immunodeficiency 52; MIM#617514). Similar duplications containing the same OMIM genes have been reported in ClinVar as Pathogenic (VarID:395931, 396629). The BP2-BP3 duplication has been identified in individuals with developmental delay, intellectual disability, and autism [PMID:27240531; PMID:32537635; PMID:30283035; PMID:21841781; PMID:19914906; PMID:19755429], although 16p11.2 distal duplications have also been observed in healthy asymptomatic individuals [PMID:27240531; PMID:30283035; PMID:19914906]. Phenotypic variability is also observed, and individuals with 16p11.2 distal duplications have been reported with additional heterogenous phenotypes including dysmorphic features, cleft lip/palate, scoliosis, and ocular findings [PMID:27240531; PMID:32537635; PMID:30283035; PMID:21841781; PMID:19914906; PMID:19755429]. Sonderby et. al [PMID:30283035] also found a correlation between individuals with the 16p11.2 distal duplication and decreased brain volume in specific regions, although additional studies are needed to confirm this finding. The inherited 16p11.2 duplication identified here is reported as a Variant of Uncertain Significance. |
| New York Genome Center | RCV001542310 | SCV001760995 | uncertain significance | not provided | 2020-07-10 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001542324 | SCV001761010 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 10 | 2020-07-03 | criteria provided, single submitter | clinical testing | The inherited 5p12 duplication identified in this individual is a duplication on the short arm of chromosome 5, which contains the first 6 exons of the HCN1 gene. The distal breakpoint of this duplication is detected at Chr5:45270314, however due to the highly repetitive nature of centromeric regions, the proximal breakpoint cannot be determined by Whole Genome Sequencing, however microarray analysis suggests this duplication extends to the centromere of chromosome 5. The only gene contained in this region is HCN1, and the distal breakpoint confirms that exons 1-6 (NM_021072.4) of the HCN1 gene are contained within this duplication. This variant is absent from gnomAD(SV_v2.1) suggesting it is not a common benign variant in the populations represented in that database. This variant is absent from ClinVar, although a duplication containing exons 1-7 has been reported in ClinVar as a Variant of UncertainSignificance (VarID:646963). To our current knowledge neither this exact variant, nor similar intergenic duplications of HCN1, have been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity and uncertainty regarding its functional consequence, the inherited 5p12 duplication containing exons 1-6 of the HCN1 gene is reported as a Variant of Uncertain Significance. |
| New York Genome Center | RCV001542377 | SCV001761070 | uncertain significance | not provided | 2020-05-29 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001542382 | SCV001761077 | likely pathogenic | Galactosylceramide beta-galactosidase deficiency | 2020-07-03 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001542388 | SCV001761085 | pathogenic | not provided | 2020-07-17 | criteria provided, single submitter | clinical testing | To our current knowledge, the exact duplication observed in this individual has not been previously reported in the literature, however the exact breakpoints of many 16q duplications reported in historical literature were not characterized by molecular methods and the exact breakpoints are uncertain. However, individuals with duplications similar to the one identified here (dup(16q11.2q21)) have been described with developmental delay, dysmorphic facial features, speech delay, intellectual disability, and additional variable features including recurrent infections, behavioral abnormalities, hyper-or hypotonia, and MRI abnormalities [PMID:21674840; PMID:22921637]. Additional individuals have been reported with proximal (16q11-q13) duplications contained within the larger duplication identified here with clinical phenotypes including developmental delay, variable intellectual disability or learning difficulties, variable dysmorphic features, speech delay, and behavioral abnormalities [PMID:16954678; PMID:10999840]. Given its presence de novo in this individual, absence in population databases, observation of several individuals with similar duplications in the literature, and its genomic content, the de novo 14.8MB duplication 16q11.2-q21 identified here is reported here as Pathogenic. |
| New York Genome Center | RCV001542403 | SCV001761102 | uncertain significance | Intellectual disability, X-linked 21 | 2020-07-17 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001542404 | SCV001761103 | uncertain significance | Epileptic encephalopathy, early infantile, 26 | 2020-07-03 | criteria provided, single submitter | clinical testing | The inherited 20q13.13 duplication is a 197.7Kb tandem duplication on the long arm of chromosome 20 thta contains four OMIM associated protein-coding genes including full duplication of DDX27 and ZNFX1, as well as partial duplication of STAU1 and KCNB1. To our current knowledge, the duplication identified in this individual has not been reported in affected individuals the literature. Of the four OMIM associated protein-coding genes within this duplication, only KCNB1is disease associated. KCNB1gene consists of a total of two exons that encode a protein of 858 amino acids. This duplication contains exon 2 (but not exon 1) of the KCNB1 gene. The ClinVar database contains a 366.9 kb duplication that involves the exon 2 of KCNB1 (i.e. partial duplication of KCNB1, ClinVar variation ID:146041), and is classified as a variant of uncertain significance. The exact duplication identified in this individual has not been reported in the literature. Given the uncertainty regarding the functional consequencesof the inherited 20q13.13 duplication it is reported as a Variant of Uncertain Significance. |
| New York Genome Center | RCV001542428 | SCV001761130 | uncertain significance | Kleefstra syndrome 2 | 2020-06-26 | criteria provided, single submitter | clinical testing | The inherited 349 kb duplication results in duplication of the first 38 exons (of 59) of the KMT2C gene. The majority of pathogenic variants in KMT2C are nonsense or frameshift [3,4], suggesting loss-of-function is the likely mechanism of disease. Moreover, ClinGen Dosage Sensitivity curation [5] indicates that the KMT2C gene has haploinsufficiency score of 3 (i.e. sufficient evidence for haploinsufficiency) whereas triplosensitivity score is zero (i.e., no evidence for triplosensitivity). There are no additional protein coding genes located within this duplication. Based on the available evidence, the 349 kb duplication inherited from an asymptomatic parent is assessed as a variant of uncertain significance. |
| New York Genome Center | RCV001542429 | SCV001761131 | uncertain significance | not provided | 2020-06-26 | criteria provided, single submitter | clinical testing | |
| Institute of Medical Genetics and Applied Genomics, |
RCV001543588 | SCV001762260 | likely pathogenic | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544701 | SCV001763879 | likely benign | not provided | 2019-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544765 | SCV001763961 | likely benign | not provided | 2018-09-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544792 | SCV001763991 | likely benign | not provided | 2019-06-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544915 | SCV001764139 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544930 | SCV001764158 | likely benign | not provided | 2018-12-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544952 | SCV001764183 | likely benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544961 | SCV001764193 | likely benign | not provided | 2019-08-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001544965 | SCV001764197 | likely benign | not provided | 2021-01-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545111 | SCV001764375 | likely benign | not provided | 2019-09-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545124 | SCV001764393 | likely benign | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545174 | SCV001764452 | likely benign | not provided | 2018-07-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545245 | SCV001764537 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545287 | SCV001764593 | likely benign | not provided | 2019-09-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545302 | SCV001764612 | likely benign | not provided | 2018-10-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545313 | SCV001764624 | likely benign | not provided | 2018-09-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545319 | SCV001764633 | likely benign | not provided | 2019-12-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545500 | SCV001764842 | likely benign | not provided | 2018-09-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545649 | SCV001765025 | likely benign | not provided | 2019-06-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545659 | SCV001765036 | likely benign | not provided | 2018-08-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545667 | SCV001765045 | likely benign | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001545923 | SCV001765345 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546017 | SCV001765457 | likely benign | not provided | 2019-08-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546105 | SCV001765561 | likely benign | not provided | 2019-02-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546195 | SCV001765671 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546200 | SCV001765678 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546330 | SCV001765826 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546341 | SCV001765838 | likely benign | not provided | 2019-08-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546401 | SCV001765911 | likely benign | not provided | 2019-09-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546440 | SCV001765958 | likely benign | not provided | 2019-08-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546445 | SCV001765965 | likely benign | not provided | 2019-09-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546488 | SCV001766015 | likely benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546545 | SCV001766077 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546549 | SCV001766081 | likely benign | not provided | 2018-08-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546650 | SCV001766202 | likely benign | not provided | 2018-06-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546725 | SCV001766296 | likely benign | not provided | 2018-08-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546739 | SCV001766314 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546757 | SCV001766335 | likely benign | not provided | 2018-10-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546772 | SCV001766352 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546798 | SCV001766382 | likely benign | not provided | 2018-11-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546864 | SCV001766461 | likely benign | not provided | 2018-10-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546871 | SCV001766468 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001546977 | SCV001766593 | likely benign | not provided | 2018-08-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547035 | SCV001766654 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547063 | SCV001766685 | likely benign | not provided | 2018-08-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547121 | SCV001766751 | likely benign | not provided | 2019-11-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547191 | SCV001766839 | likely benign | not provided | 2018-06-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547206 | SCV001766856 | likely benign | not provided | 2019-07-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547274 | SCV001766938 | likely benign | not provided | 2018-11-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547302 | SCV001766971 | likely benign | not provided | 2018-08-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547322 | SCV001766994 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547352 | SCV001767037 | likely benign | not provided | 2018-09-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547363 | SCV001767050 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547368 | SCV001767056 | likely benign | not provided | 2019-08-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547390 | SCV001767083 | likely benign | not provided | 2019-05-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547525 | SCV001767257 | likely benign | not provided | 2018-07-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547622 | SCV001767373 | likely benign | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547629 | SCV001767382 | likely benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547667 | SCV001767429 | likely benign | not provided | 2019-10-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547860 | SCV001767660 | likely benign | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547874 | SCV001767676 | likely benign | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001547876 | SCV001767682 | uncertain significance | not provided | 2019-07-05 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant |
| Gene |
RCV001547879 | SCV001767685 | likely benign | not provided | 2020-01-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001548003 | SCV001767845 | likely benign | not provided | 2018-12-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001548187 | SCV001768054 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001548345 | SCV001768240 | likely benign | not provided | 2018-10-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001548381 | SCV001768281 | likely benign | not provided | 2019-11-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001548386 | SCV001768288 | likely benign | not provided | 2018-09-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001548425 | SCV001768332 | likely benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549312 | SCV001769437 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549347 | SCV001769481 | likely benign | not provided | 2020-04-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549514 | SCV001769679 | likely benign | not provided | 2019-02-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549542 | SCV001769719 | likely benign | not provided | 2018-06-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549556 | SCV001769735 | likely benign | not provided | 2020-04-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549643 | SCV001769828 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549681 | SCV001769875 | likely benign | not provided | 2019-05-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549798 | SCV001770014 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549842 | SCV001770070 | likely benign | not provided | 2018-12-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549854 | SCV001770082 | likely benign | not provided | 2019-01-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549970 | SCV001770217 | likely benign | not provided | 2019-12-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550034 | SCV001770302 | likely benign | not provided | 2020-08-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550037 | SCV001770305 | likely benign | not provided | 2019-08-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550060 | SCV001770331 | likely benign | not provided | 2018-12-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550099 | SCV001770379 | likely benign | not provided | 2019-01-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550190 | SCV001770482 | likely benign | not provided | 2018-10-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550257 | SCV001770557 | likely benign | not provided | 2019-08-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550316 | SCV001770626 | likely benign | not provided | 2020-05-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550375 | SCV001770690 | likely benign | not provided | 2018-08-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550540 | SCV001770879 | likely benign | not provided | 2018-09-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550682 | SCV001771052 | likely benign | not provided | 2020-03-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550688 | SCV001771061 | likely benign | not provided | 2018-08-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550719 | SCV001771097 | likely benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550733 | SCV001771113 | likely benign | not provided | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550756 | SCV001771140 | likely benign | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550780 | SCV001771167 | likely benign | not provided | 2019-08-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550805 | SCV001771195 | likely benign | not provided | 2019-10-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550810 | SCV001771200 | likely benign | not provided | 2018-09-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550840 | SCV001771235 | likely benign | not provided | 2018-08-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550873 | SCV001771272 | likely benign | not provided | 2020-03-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550941 | SCV001771349 | likely benign | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551061 | SCV001771486 | likely benign | not provided | 2019-02-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551068 | SCV001771494 | uncertain significance | not provided | 2019-12-24 | criteria provided, single submitter | clinical testing | Describes a nucleotide substitution 900 base pairs upstream of the ATG translational start site in the PTEN promoter region; Variants within the PTEN promoter have been observed in individuals with features of Cowden syndrome (Zhou 2003); Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant; Also known as c.-899C>G; This variant is associated with the following publications: (PMID: 12844284) |
| Gene |
RCV001551124 | SCV001771560 | likely benign | not provided | 2019-05-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551176 | SCV001771629 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551177 | SCV001771630 | likely benign | not provided | 2018-09-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551248 | SCV001771715 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551302 | SCV001771781 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551351 | SCV001771837 | likely benign | not provided | 2018-08-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551364 | SCV001771853 | likely benign | not provided | 2019-09-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551403 | SCV001771907 | likely benign | not provided | 2019-08-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551489 | SCV001772010 | likely benign | not provided | 2018-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551498 | SCV001772020 | likely benign | not provided | 2018-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551531 | SCV001772055 | likely benign | not provided | 2019-08-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551571 | SCV001772102 | likely benign | not provided | 2019-08-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551578 | SCV001772112 | likely benign | not provided | 2018-08-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551620 | SCV001772161 | likely benign | not provided | 2019-05-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551679 | SCV001772238 | likely benign | not provided | 2018-07-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551766 | SCV001772339 | likely benign | not provided | 2019-04-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551881 | SCV001772478 | likely benign | not provided | 2019-10-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551940 | SCV001772548 | likely benign | not provided | 2018-07-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552020 | SCV001772634 | likely benign | not provided | 2018-06-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552046 | SCV001772662 | likely benign | not provided | 2018-12-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552178 | SCV001772825 | likely benign | not provided | 2019-08-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552187 | SCV001772835 | likely benign | not provided | 2019-12-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552207 | SCV001772857 | likely benign | not provided | 2018-06-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552271 | SCV001772929 | likely benign | not provided | 2019-11-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552359 | SCV001773031 | likely benign | not provided | 2019-06-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552397 | SCV001773075 | likely benign | not provided | 2020-03-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552417 | SCV001773099 | likely benign | not provided | 2019-10-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552505 | SCV001773203 | likely benign | not provided | 2018-08-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552509 | SCV001773208 | likely benign | not provided | 2018-08-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552559 | SCV001773265 | likely benign | not provided | 2020-02-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552659 | SCV001773387 | likely benign | not provided | 2019-11-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552762 | SCV001773512 | likely benign | not provided | 2019-04-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552823 | SCV001773587 | likely benign | not provided | 2019-12-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552967 | SCV001773751 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001552993 | SCV001773784 | likely benign | not provided | 2018-08-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553026 | SCV001773821 | likely benign | not provided | 2020-08-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553161 | SCV001773978 | likely benign | not provided | 2018-10-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553371 | SCV001774230 | likely benign | not provided | 2021-01-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553413 | SCV001774275 | likely benign | not provided | 2018-09-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553462 | SCV001774335 | likely benign | not provided | 2019-08-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553506 | SCV001774386 | likely benign | not provided | 2019-04-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001553531 | SCV001774416 | likely benign | not provided | 2019-10-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001554962 | SCV001776303 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555015 | SCV001776361 | likely benign | not provided | 2018-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555034 | SCV001776383 | likely benign | not provided | 2019-08-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555060 | SCV001776413 | likely benign | not provided | 2018-11-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555063 | SCV001776417 | likely benign | not provided | 2019-08-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555106 | SCV001776460 | likely benign | not provided | 2018-08-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555164 | SCV001776531 | likely benign | not provided | 2018-10-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555173 | SCV001776542 | likely benign | not provided | 2020-01-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555183 | SCV001776554 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555231 | SCV001776611 | likely benign | not provided | 2018-06-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555310 | SCV001776703 | likely benign | not provided | 2018-08-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555360 | SCV001776768 | likely benign | not provided | 2019-10-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555513 | SCV001776949 | likely benign | not provided | 2018-09-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555519 | SCV001776957 | likely benign | not provided | 2018-07-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555633 | SCV001777081 | likely benign | not provided | 2018-11-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555638 | SCV001777086 | likely benign | not provided | 2018-10-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555643 | SCV001777092 | likely benign | not provided | 2018-08-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555674 | SCV001777126 | likely benign | not provided | 2018-08-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555757 | SCV001777220 | likely benign | not provided | 2018-08-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555759 | SCV001777222 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555776 | SCV001777243 | uncertain significance | not provided | 2021-06-23 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Located in a region that tolerates variation and lacks pathogenic variants; This variant is associated with the following publications: (PMID: 27535533) |
| Gene |
RCV001555801 | SCV001777270 | likely benign | not provided | 2019-04-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555836 | SCV001777312 | likely benign | not provided | 2019-09-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555865 | SCV001777350 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555898 | SCV001777388 | likely benign | not provided | 2018-10-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001555929 | SCV001777422 | likely benign | not provided | 2019-08-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556044 | SCV001777556 | likely benign | not provided | 2019-04-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556161 | SCV001777691 | likely benign | not provided | 2018-10-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556195 | SCV001777730 | likely benign | not provided | 2019-09-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556299 | SCV001777857 | likely benign | not provided | 2018-10-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556303 | SCV001777861 | likely benign | not provided | 2018-10-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556437 | SCV001778019 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556617 | SCV001778230 | likely benign | not provided | 2018-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556666 | SCV001778287 | uncertain significance | not provided | 2020-08-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
| Gene |
RCV001556691 | SCV001778318 | likely benign | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556813 | SCV001778460 | likely benign | not provided | 2019-10-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556867 | SCV001778523 | likely benign | not provided | 2019-10-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001556910 | SCV001778575 | likely benign | not provided | 2018-09-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557127 | SCV001778831 | likely benign | not provided | 2019-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557246 | SCV001778973 | likely benign | not provided | 2019-10-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557254 | SCV001778982 | likely benign | not provided | 2019-02-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557275 | SCV001779006 | likely benign | not provided | 2019-10-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557331 | SCV001779078 | likely benign | not provided | 2018-11-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557374 | SCV001779127 | likely benign | not provided | 2018-12-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557494 | SCV001779265 | likely benign | not provided | 2019-03-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557621 | SCV001779413 | likely benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557687 | SCV001779494 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557996 | SCV001779857 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558046 | SCV001779917 | likely benign | not provided | 2019-06-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558158 | SCV001780047 | likely benign | not provided | 2019-07-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558162 | SCV001780051 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558168 | SCV001780058 | likely benign | not provided | 2019-02-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558224 | SCV001780125 | likely benign | not provided | 2019-06-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558289 | SCV001780203 | likely benign | not provided | 2019-09-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558524 | SCV001780489 | likely benign | not provided | 2020-01-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558571 | SCV001780549 | likely benign | not provided | 2019-01-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558610 | SCV001780598 | likely benign | not provided | 2020-04-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558628 | SCV001780619 | likely benign | not provided | 2018-08-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558670 | SCV001780667 | likely benign | not provided | 2019-11-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558672 | SCV001780669 | likely benign | not provided | 2019-05-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558682 | SCV001780681 | likely benign | not provided | 2020-01-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558775 | SCV001780791 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558814 | SCV001780835 | likely benign | not provided | 2020-12-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558822 | SCV001780845 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558867 | SCV001780898 | likely benign | not provided | 2019-06-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558910 | SCV001780952 | likely benign | not provided | 2018-06-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001558968 | SCV001781016 | likely benign | not provided | 2020-02-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559346 | SCV001781560 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559350 | SCV001781564 | likely benign | not provided | 2019-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559360 | SCV001781574 | likely benign | not provided | 2020-04-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559420 | SCV001781639 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559499 | SCV001781736 | likely benign | not provided | 2019-03-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559524 | SCV001781763 | likely benign | not provided | 2018-09-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559564 | SCV001781817 | likely benign | not provided | 2019-03-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559616 | SCV001781886 | likely benign | not provided | 2018-10-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559682 | SCV001781966 | likely benign | not provided | 2019-06-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559707 | SCV001781997 | likely benign | not provided | 2019-08-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559800 | SCV001782099 | likely benign | not provided | 2019-02-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559940 | SCV001782266 | likely benign | not provided | 2020-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001559957 | SCV001782285 | likely benign | not provided | 2019-04-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560006 | SCV001782336 | likely benign | not provided | 2018-08-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560058 | SCV001782392 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560098 | SCV001782438 | likely benign | not provided | 2018-10-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560177 | SCV001782533 | likely benign | not provided | 2018-08-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560315 | SCV001782701 | likely benign | not provided | 2018-11-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560319 | SCV001782705 | likely benign | not provided | 2019-08-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560365 | SCV001782763 | likely benign | not provided | 2020-02-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560425 | SCV001782838 | likely benign | not provided | 2018-07-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560464 | SCV001782882 | likely benign | not provided | 2018-07-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560544 | SCV001782975 | likely benign | not provided | 2020-08-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560574 | SCV001783011 | likely benign | not provided | 2018-08-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560622 | SCV001783074 | likely benign | not provided | 2019-06-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560694 | SCV001783155 | likely benign | not provided | 2018-06-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560704 | SCV001783167 | likely benign | not provided | 2019-04-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560728 | SCV001783196 | likely benign | not provided | 2018-06-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560854 | SCV001783345 | likely benign | not provided | 2019-04-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560943 | SCV001783451 | likely benign | not provided | 2018-09-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001560995 | SCV001783511 | likely benign | not provided | 2019-08-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561057 | SCV001783584 | likely benign | not provided | 2018-12-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561072 | SCV001783603 | likely benign | not provided | 2019-11-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561075 | SCV001783607 | likely benign | not provided | 2019-11-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561115 | SCV001783652 | likely benign | not provided | 2019-06-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561377 | SCV001783975 | likely benign | not provided | 2019-08-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561414 | SCV001784017 | likely benign | not provided | 2018-08-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561451 | SCV001784060 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561467 | SCV001784077 | likely benign | not provided | 2019-10-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561657 | SCV001784295 | likely benign | not provided | 2019-08-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561666 | SCV001784306 | likely benign | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561902 | SCV001784588 | likely benign | not provided | 2018-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561904 | SCV001784591 | likely benign | not provided | 2018-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561937 | SCV001784627 | likely benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001561979 | SCV001784677 | likely benign | not provided | 2020-07-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562195 | SCV001784925 | likely benign | not provided | 2019-11-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562241 | SCV001784977 | likely benign | not provided | 2019-01-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562378 | SCV001785133 | likely benign | not provided | 2019-12-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562479 | SCV001785249 | likely benign | not provided | 2019-11-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562518 | SCV001785294 | likely benign | not provided | 2018-08-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562702 | SCV001785508 | likely benign | not provided | 2019-10-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562755 | SCV001785570 | likely benign | not provided | 2018-08-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562873 | SCV001785710 | likely benign | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562887 | SCV001785726 | likely benign | not provided | 2019-11-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562888 | SCV001785727 | likely benign | not provided | 2020-11-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562903 | SCV001785745 | likely benign | not provided | 2020-12-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001562914 | SCV001785760 | likely benign | not provided | 2018-10-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001563075 | SCV001785953 | likely benign | not provided | 2019-04-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001563095 | SCV001785977 | likely benign | not provided | 2018-09-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001563109 | SCV001785993 | likely benign | not provided | 2018-07-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001563122 |