ClinVar Miner

Submissions for variant Single allele (rs1553673680)

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Total submissions: 5089
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Developmental Genetics Unit,King Faisal Specialist Hospital & Research Centre RCV000171541 SCV000221740 likely pathogenic not provided criteria provided, single submitter research
Dobyns Lab,Seattle Children's Research Institute RCV000191932 SCV000246158 pathogenic Poretti-Boltshauser syndrome 2014-11-25 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine 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,Oxford University Hospitals NHS Foundation Trust RCV000210049 SCV000257461 pathogenic Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2015-08-25 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203452 SCV000258328 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203475 SCV000258329 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203496 SCV000258330 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203458 SCV000258331 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203474 SCV000258332 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203463 SCV000258334 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203486 SCV000258335 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203462 SCV000258337 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203484 SCV000258338 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203447 SCV000258339 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203468 SCV000258340 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203483 SCV000258341 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203451 SCV000258342 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203466 SCV000258343 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203489 SCV000258344 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203456 SCV000258345 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203472 SCV000258346 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203499 SCV000258350 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203453 SCV000258351 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203460 SCV000258354 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203481 SCV000258355 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203495 SCV000258356 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203464 SCV000258357 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203480 SCV000258358 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203449 SCV000258359 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203485 SCV000258361 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203448 SCV000258362 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203469 SCV000258363 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203491 SCV000258364 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203459 SCV000258365 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203467 SCV000258366 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203490 SCV000258367 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203473 SCV000258369 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203488 SCV000258370 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203492 SCV000258373 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203498 SCV000258376 pathogenic Spastic paraplegia 4, autosomal dominant 2014-08-07 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203289 SCV000258388 likely pathogenic Bosch-Boonstra-Schaaf optic atrophy syndrome 2014-02-06 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine RCV000210394 SCV000258457 pathogenic Chromosome 17p13.1 deletion syndrome 2015-11-06 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000210404 SCV000258458 pathogenic Chromosome 17p13.1 deletion syndrome 2015-11-06 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000210387 SCV000258459 pathogenic Chromosome 17p13.1 deletion syndrome 2015-11-06 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000210397 SCV000258460 pathogenic Chromosome 17p13.1 deletion syndrome 2015-11-06 criteria provided, single submitter research
Ludwig Lab, Institute of Human Genetics, University Hospital Bonn RCV000417195 SCV000262654 likely pathogenic Currarino triad criteria provided, single submitter research Large de novo duplication in a patient with negative family history.
Elsea Laboratory,Baylor College of Medicine RCV000455872 SCV000264470 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000454803 SCV000264471 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000455222 SCV000264472 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000455812 SCV000264473 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000454759 SCV000264474 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000477897 SCV000264477 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000454618 SCV000264478 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000477751 SCV000264479 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Elsea Laboratory,Baylor College of Medicine RCV000455254 SCV000264480 pathogenic MBD5 associated neurodevelopmental disorder 2012-10-01 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000210384 SCV000266398 pathogenic Immunodeficiency 23 2014-07-03 criteria provided, single submitter research segregates with the phenotype in an affected family
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000210452 SCV000266536 pathogenic Loeys-Dietz syndrome 4 criteria provided, single submitter research
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000210464 SCV000266537 pathogenic Loeys-Dietz syndrome 4 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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,Children's Mercy Hospital and Clinics RCV000224569 SCV000281025 uncertain significance not provided 2015-12-22 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Geschwind lab,University of California Los Angeles RCV000225569 SCV000282087 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225670 SCV000282088 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225439 SCV000282089 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225548 SCV000282090 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225681 SCV000282091 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225457 SCV000282092 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225542 SCV000282093 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225679 SCV000282094 likely pathogenic Autism spectrum disorder criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225451 SCV000282095 likely pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225595 SCV000282096 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225368 SCV000282097 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225469 SCV000282098 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225572 SCV000282099 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225402 SCV000282100 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225508 SCV000282101 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225645 SCV000282102 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225379 SCV000282103 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225522 SCV000282104 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles 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,University of California Los Angeles RCV000225436 SCV000282106 likely pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225546 SCV000282107 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225619 SCV000282108 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225434 SCV000282109 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225539 SCV000282110 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225676 SCV000282111 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225448 SCV000282112 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225559 SCV000282113 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225649 SCV000282114 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225471 SCV000282115 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225587 SCV000282116 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225404 SCV000282117 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225463 SCV000282118 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225607 SCV000282119 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225377 SCV000282120 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225525 SCV000282121 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225621 SCV000282122 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225398 SCV000282123 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225516 SCV000282124 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225620 SCV000282125 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225430 SCV000282126 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225540 SCV000282127 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225633 SCV000282128 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225410 SCV000282129 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225556 SCV000282130 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225671 SCV000282131 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225446 SCV000282132 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225549 SCV000282133 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225687 SCV000282134 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225459 SCV000282135 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225604 SCV000282136 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles 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,University of California Los Angeles RCV000225479 SCV000282138 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225596 SCV000282139 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225373 SCV000282140 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225512 SCV000282141 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225576 SCV000282142 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225386 SCV000282143 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225492 SCV000282144 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225630 SCV000282145 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles 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,University of California Los Angeles 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,University of California Los Angeles RCV000225629 SCV000282148 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225442 SCV000282149 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225550 SCV000282150 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225685 SCV000282151 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225421 SCV000282158 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225563 SCV000282159 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225663 SCV000282160 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225455 SCV000282161 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225599 SCV000282162 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225655 SCV000282163 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225476 SCV000282164 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225574 SCV000282165 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225391 SCV000282166 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225489 SCV000282167 likely pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225609 SCV000282168 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225382 SCV000282169 pathogenic Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225526 SCV000282170 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225626 SCV000282171 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225438 SCV000282172 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225497 SCV000282173 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225644 SCV000282174 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225420 SCV000282175 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225541 SCV000282176 association Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225635 SCV000282177 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225416 SCV000282178 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225562 SCV000282179 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225652 SCV000282180 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225468 SCV000282181 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225537 SCV000282182 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225674 SCV000282183 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225465 SCV000282184 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225606 SCV000282185 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225383 SCV000282186 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Geschwind lab,University of California Los Angeles RCV000225486 SCV000282187 uncertain significance Autism spectrum disorder 2015-10-12 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000234859 SCV000291989 pathogenic Syndromic X-linked intellectual disability Lubs type 2015-03-13 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000234878 SCV000291990 pathogenic Syndromic X-linked intellectual disability Lubs type 2015-03-13 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine RCV000235042 SCV000292317 pathogenic Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 2015-11-12 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine 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, Baylor-Hopkins CMG, Baylor College of Medicine 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000385479 SCV000330986 likely benign not specified 2015-09-29 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000299568 SCV000331783 uncertain significance not provided 2016-01-28 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000318149 SCV000334678 uncertain significance not provided 2015-08-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000273531 SCV000335444 uncertain significance not provided 2015-09-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000337319 SCV000336997 likely pathogenic not provided 2015-10-26 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000400412 SCV000340516 pathogenic not provided 2016-03-18 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000349357 SCV000340741 uncertain significance not provided 2016-04-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000309059 SCV000340769 likely benign not specified 2016-04-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000299738 SCV000341602 uncertain significance not provided 2016-05-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000308584 SCV000341702 uncertain significance not provided 2016-05-18 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000315072 SCV000341808 uncertain significance not provided 2016-06-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000278127 SCV000341988 uncertain significance not provided 2016-05-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000340414 SCV000343758 uncertain significance not provided 2016-07-12 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000292125 SCV000344235 benign not specified 2016-08-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000393096 SCV000483466 likely benign Myopathy, distal, 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000304800 SCV000483467 likely benign Myosin storage myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000341222 SCV000483468 likely benign Scapuloperoneal myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000393119 SCV000483469 likely benign Cardiomyopathy, left ventricular noncompaction 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000310759 SCV000483470 likely benign Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000365436 SCV000483471 likely benign Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000261807 SCV000483973 likely benign Myosclerosis, autosomal recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000330899 SCV000483974 likely benign Collagen VI-related myopathy 2016-06-14 criteria provided, single submitter clinical testing
Robarts Research Institute,Western University RCV000408813 SCV000484813 likely pathogenic Familial hypercholesterolemia 1 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge 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 (CIMBA), c/o University of Cambridge 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 (CIMBA), c/o University of Cambridge 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 (CIMBA), c/o University of Cambridge 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 (CIMBA), c/o University of Cambridge 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 (CIMBA), c/o University of Cambridge RCV000414360 SCV000490175 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414960 SCV000492733 pathogenic Renal cyst; Pancreatic cysts 2015-09-23 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000415472 SCV000493131 likely pathogenic Chromosome Xq26.3 duplication syndrome 2016-01-01 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000415468 SCV000493132 likely pathogenic Chromosome Xq26.3 duplication syndrome 2016-01-01 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000415470 SCV000493133 likely pathogenic Chromosome Xq26.3 duplication syndrome 2016-01-01 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000415471 SCV000493134 likely pathogenic Chromosome Xq26.3 duplication syndrome 2016-01-01 criteria provided, single submitter research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine 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 - MEYER, AOU Meyer RCV000416971 SCV000494569 pathogenic Epileptic encephalopathy 2016-11-16 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics 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,Children's Mercy Hospital and Clinics RCV000426740 SCV000511008 uncertain significance not provided 2017-01-16 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Knight Diagnostic Laboratories, Oregon Health and Sciences University 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, Oregon Health and Sciences University 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, Oregon Health and Sciences University 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, Oregon Health and Sciences University 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,Nationwide Children's Hospital 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-Suei Laboratory,Academia Sinica 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.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000500418 SCV000598154 pathogenic Hereditary hemorrhagic telangiectasia type 1 2016-08-04 criteria provided, single submitter clinical testing
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505253 SCV000599309 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505214 SCV000599316 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505243 SCV000599317 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505182 SCV000599318 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505219 SCV000599319 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505246 SCV000599320 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506174 SCV000605444 uncertain significance not specified 2017-03-10 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital 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)
Undiagnosed Diseases Network,NIH 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, Clinical Genetics,Karolinska Institutet 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, Broad Institute 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).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000594755 SCV000703106 uncertain significance not provided 2017-02-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000592422 SCV000703422 uncertain significance not provided 2017-01-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000593500 SCV000704742 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000597577 SCV000706542 uncertain significance not provided 2017-02-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000597921 SCV000707424 uncertain significance not provided 2017-03-30 criteria provided, single submitter clinical testing
GeneDx 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, Dr. Klein, Dr. Rost and Colleagues RCV000624863 SCV000740317 pathogenic Spherocytosis type 2 2018-03-29 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne 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, Université de Bourgogne 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, Université de Bourgogne RCV000627117 SCV000747921 likely pathogenic Autistic behavior; Moderate global developmental delay 2017-05-27 criteria provided, single submitter clinical testing
Department of Psychiatry,Nagoya University RCV000754118 SCV000777921 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754119 SCV000777922 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754124 SCV000777927 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754129 SCV000777932 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754131 SCV000777934 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754132 SCV000777935 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754147 SCV000777950 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754155 SCV000777958 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754156 SCV000777959 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754157 SCV000777960 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754158 SCV000777961 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754160 SCV000777963 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754162 SCV000777965 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754164 SCV000777967 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754166 SCV000777969 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754167 SCV000777970 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754168 SCV000777971 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754171 SCV000777974 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754172 SCV000777975 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754173 SCV000777976 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754174 SCV000777977 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754175 SCV000777978 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754177 SCV000777980 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754179 SCV000777982 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754180 SCV000777983 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754182 SCV000777985 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754184 SCV000777987 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754185 SCV000777988 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754186 SCV000777989 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754188 SCV000777991 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754189 SCV000777992 pathogenic Autistic disorder of childhood onset; Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754201 SCV000778004 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754205 SCV000778008 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754211 SCV000778014 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754212 SCV000778015 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754229 SCV000778032 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754248 SCV000778051 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754249 SCV000778052 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754250 SCV000778053 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754256 SCV000778059 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754258 SCV000778061 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754259 SCV000778062 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754267 SCV000778070 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754277 SCV000778080 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754283 SCV000778086 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754289 SCV000778092 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754292 SCV000778095 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754324 SCV000778127 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754329 SCV000778132 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754330 SCV000778133 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754331 SCV000778134 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754332 SCV000778135 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754333 SCV000778136 pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754334 SCV000778137 pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754346 SCV000778149 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754347 SCV000778150 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754348 SCV000778151 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754349 SCV000778152 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754350 SCV000778153 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754351 SCV000778154 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754352 SCV000778155 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754353 SCV000778156 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754362 SCV000778165 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754363 SCV000778166 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754364 SCV000778167 likely pathogenic Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754365 SCV000778168 pathogenic Autistic disorder of childhood onset; Schizophrenia 2018-03-20 criteria provided, single submitter research
Department of Psychiatry,Nagoya University RCV000754378 SCV000778181 likely pathogenic Autistic disorder of childhood onset 2018-03-20 criteria provided, single submitter research
Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano RCV000754403 SCV000787664 uncertain significance Primary amenorrhea 2018-06-01 criteria provided, single submitter research
Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano RCV000754413 SCV000787674 likely benign Primary amenorrhea 2018-06-01 criteria provided, single submitter research
Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano RCV000754469 SCV000787730 uncertain significance Primary amenorrhea 2018-06-01 criteria provided, single submitter research
Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano RCV000754473 SCV000787734 likely benign Primary amenorrhea 2018-06-01 criteria provided, single submitter research
Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano RCV000754474 SCV000787735 uncertain significance Primary amenorrhea 2018-06-01 criteria provided, single submitter research
Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano RCV000754479 SCV000787740 uncertain significance Primary amenorrhea 2018-06-01 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000754946 SCV000788371 pathogenic Jeune thoracic dystrophy 2018-05-01 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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, Clinical Genetics,Karolinska Institutet RCV000754985 SCV000803395 uncertain significance Congenital malrotation of intestine 2018-06-11 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000754990 SCV000803400 pathogenic Congenital malrotation of intestine 2018-06-11 criteria provided, single submitter research
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System RCV000678004 SCV000804159 uncertain significance Autistic disorder of childhood onset 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System RCV000678010 SCV000804165 uncertain significance Autistic disorder of childhood onset 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Geisinger Health System 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,Baylor College of Medicine 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, Policlinico S. Orsola.Malpighi 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,NIH RCV000708570 SCV000837689 pathogenic Cornelia de Lange syndrome 5 2018-03-16 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV000708593 SCV000837720 likely pathogenic Combined oxidative phosphorylation deficiency 31 2018-01-04 criteria provided, single submitter clinical testing
Genetics - Viapath,Viapath, Guy's Hospital 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 - Viapath,Viapath, Guy's Hospital 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000730072 SCV000857783 uncertain significance not provided 2017-10-24 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000734617 SCV000862771 other not provided 2018-08-06 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV000735205 SCV000863411 uncertain significance Branched-chain keto acid dehydrogenase kinase deficiency 2018-03-16 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH 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,NIH RCV000735211 SCV000863419 pathogenic Early infantile epileptic encephalopathy 4 2017-10-23 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV000735212 SCV000863420 pathogenic Deafness-infertility syndrome 2017-11-14 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH 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,NIH 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,IRCCS Istituto Auxologico Italiano RCV000785663 SCV000863549 uncertain significance Silver Russell Syndrome-related disorder 2018-12-06 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735898 SCV000864010 uncertain significance Trichorhinophalangeal dysplasia type I 2018-12-17 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735899 SCV000864011 uncertain significance Trichorhinophalangeal dysplasia type I 2018-12-17 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735900 SCV000864012 pathogenic Trichorhinophalangeal dysplasia type I 2018-12-17 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735901 SCV000864013 pathogenic Hypoparathyroidism, deafness, renal disease syndrome 2018-12-17 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735904 SCV000864016 uncertain significance Cerebellar ataxia, nonprogressive, with mental retardation 2018-12-17 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735905 SCV000864017 benign Cerebellar ataxia, nonprogressive, with mental retardation 2018-12-17 criteria provided, single submitter research
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000735906 SCV000864018 uncertain significance Cerebellar ataxia, nonprogressive, with mental retardation 2018-12-17 criteria provided, single submitter research
Raymond Lab,University of Cambridge RCV000850220 SCV000897737 pathogenic Intellectual disability 2019-02-13 criteria provided, single submitter research
Department of Clinical Genetics,Tartu University Hospital RCV000768549 SCV000898485 pathogenic Dihydropteridine reductase deficiency 2019-04-20 criteria provided, single submitter research
Biochemistry Laboratory of CDMU,Chengde Medical University RCV000768460 SCV000899223 likely pathogenic not provided criteria provided, single submitter case-control
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852264 SCV000900011 likely pathogenic Hereditary factor IX deficiency disease 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852268 SCV000900013 likely pathogenic Antithrombin III deficiency 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852266 SCV000900014 likely pathogenic Hereditary factor X deficiency disease 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852267 SCV000900015 likely pathogenic Abnormal bleeding 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852274 SCV000900016 uncertain significance Abnormal bleeding 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852258 SCV000900022 likely pathogenic 11q partial monosomy syndrome 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852273 SCV000900024 pathogenic Macrothrombocytopenia 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852269 SCV000900025 likely pathogenic Thrombocytopenia 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852261 SCV000900027 likely pathogenic Antithrombin III deficiency 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852271 SCV000900030 likely pathogenic Deep venous thrombosis 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852272 SCV000900031 likely pathogenic Protein S deficiency disease 2019-02-01 criteria provided, single submitter research
Undiagnosed Diseases Network,NIH 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,NIH 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 (chr5:127441491‐127471419delins34). As a carrier, the father shows no symptoms of Kilquist syndrome. This family has been reported in PMID: 30740830.
Undiagnosed Diseases Network,NIH RCV000791288 SCV000930566 likely pathogenic Kleefstra syndrome 2 2017-12-15 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000824954 SCV000965989 pathogenic Intellectual disability, severe 2016-01-01 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000824957 SCV000965998 pathogenic Marfan syndrome 2016-01-01 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne 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, Université de Bourgogne RCV000825026 SCV000966221 pathogenic Chromosome 15q11-q13 duplication syndrome 2018-10-16 criteria provided, single submitter clinical testing
Academic Department of Medical Genetics, University of Cambridge RCV000850066 SCV000992232 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research
Academic Department of Medical Genetics, University of Cambridge RCV000850067 SCV000992233 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research
Academic Department of Medical Genetics, University of Cambridge RCV000850068 SCV000992234 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research
Academic Department of Medical Genetics, University of Cambridge RCV000850149 SCV000992322 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research
Academic Department of Medical Genetics, University of Cambridge 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
UT Southwestern Medical Center, UT Southwestern Medical Center RCV000853070 SCV000992360 drug response Imatinib response 2019-09-09 criteria provided, single submitter clinical testing The variant in PDGRFB has been reported in a patient with multi focal infantile myofibromatosis (Hassan 2019) and was reported to be activating, tumorigenic in mice, and sensitive to imatinib in vitro. Review of this variant suggests a complicated deletion/duplication in which 13 nt are deleted from within exon 12 (breakpoints Chr 5: 149,505,080, Chr 5:149,505,067) and replaced by a duplicated portion of intron 14 and exon 15 (breakpoints intron 14-Chr 5: 149,502,780, exon 15-Chr 5:F2 149,502,629)
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine 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, Molecular and Human Genetics, Baylor College of Medicine 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, Molecular and Human Genetics, Baylor College of Medicine 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, Molecular and Human Genetics, Baylor College of Medicine 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, Université de Bourgogne RCV000851176 SCV000993410 likely pathogenic Marfanoid habitus and intellectual disability criteria provided, single submitter research
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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.
GeneDx 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, Baylor College of Medicine 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.
GeneDx 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, Royal College of Surgeons in Ireland RCV001031017 SCV001160792 pathogenic 16p11.2 deletion syndrome 2019-12-11 criteria provided, single submitter research
Broad Institute Rare Disease Group, Broad Institute 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, University of Cambridge RCV001027727 SCV001190163 pathogenic Common variable agammaglobulinemia 2019-01-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV001027728 SCV001190164 pathogenic Common variable agammaglobulinemia 2019-01-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV001027643 SCV001190215 likely pathogenic Inherited Immunodeficiency Diseases 2019-01-01 criteria provided, single submitter research
Central Laboratory,The First Hospital of Lanzhou University 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 stromal 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 Fabry disease 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, Alberta Children's Hospital RCV001095544 SCV001245472 likely pathogenic Hiatal 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,NIH 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,NIH 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, Broad Institute 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,Washington University in St. Louis 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, University of Adelaide 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,Garvan Institute of Medical Research RCV001254216 SCV001430285 pathogenic Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV001254217 SCV001430286 pathogenic Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV001254247 SCV001430287 pathogenic Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV001256004 SCV001430883 pathogenic Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
Undiagnosed Diseases Network,NIH 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,NIH RCV001255610 SCV001432136 uncertain significance Wolf-Hirschhorn like syndrome 2020-05-07 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV001255967 SCV001432743 uncertain significance ELFN1-related condition 2018-09-18 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV001255970 SCV001432747 pathogenic Epileptic encephalopathy, early infantile, 28 2020-07-08 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV001255971 SCV001432748 pathogenic Wieacker-Wolff syndrome, female-restricted 2020-05-26 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV001255972 SCV001432749 pathogenic Koolen-de Vries syndrome 2020-05-29 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, University of Torino 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, INGEBI / CONICET 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, INGEBI / CONICET 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, Rady Children's Hospital San Diego 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, Rady Children's Hospital San Diego 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, Rady Children's Hospital San Diego 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, University of Cambridge RCV001262039 SCV001439417 pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research PVS1+PM2+PP4
NIHR Bioresource Rare Diseases, University of Cambridge RCV001262041 SCV001439419 pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research PVS1+PM2+PP4
NIHR Bioresource Rare Diseases, University of Cambridge RCV001262047 SCV001439425 pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research PVS1+PM2+PP4
Center for Statistical Genetics, Columbia University RCV001261860 SCV001448212 pathogenic Intellectual disability 2020-10-16 criteria provided, single submitter research
Bertuch Lab,Baylor College of Medicine 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. Genetics and Cancer, Menzies Institute for Medical Research,University of Tasmania RCV001376650 SCV001450780 likely benign Congenital cataract 2020-12-01 criteria provided, single submitter research
Dept. Genetics and Cancer, Menzies Institute for Medical Research,University of Tasmania RCV001376651 SCV001450781 likely benign Congenital cataract 2020-12-01 criteria provided, single submitter research
Institute of Medical Molecular Genetics, University of Zurich RCV001270921 SCV001451705 pathogenic Congenital miosis 2020-12-21 criteria provided, single submitter clinical testing
Center for Statistical Genetics, Columbia University 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,NIH RCV001310223 SCV001499834 pathogenic Immunodeficiency 67 2020-11-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001311002 SCV001501010 likely benign not provided 2020-07-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001311736 SCV001502028 likely benign not provided 2021-01-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001311737 SCV001502029 uncertain significance not provided 2020-10-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen 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, Children’s Hospital of Fudan University RCV001352677 SCV001519656 likely pathogenic Inflammatory bowel disease 28, autosomal recessive 2021-01-17 criteria provided, single submitter clinical testing
GeneDx 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,University of Padova RCV001578513 SCV001547742 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Absent from gnomAD v2.1.1 (PM2_moderate)
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin RCV001353222 SCV001548365 pathogenic Cohen syndrome 2021-03-30 criteria provided, single submitter research
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391666 SCV001593290 pathogenic Syndromic X-linked intellectual disability Lubs type 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391667 SCV001593291 pathogenic Deletion of short arm of chromosome 18 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University 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,The First Affiliated Hospital of Zhengzhou University RCV001391669 SCV001593293 pathogenic not provided 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391670 SCV001593294 pathogenic Chromosome 10q26 deletion syndrome 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391671 SCV001593295 pathogenic 16p11.2 deletion syndrome 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391672 SCV001593296 pathogenic DiGeorge Syndrome 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391673 SCV001593297 pathogenic Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391674 SCV001593298 likely pathogenic Chromosome 15q26-qter deletion syndrome 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391675 SCV001593299 pathogenic DiGeorge Syndrome 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391676 SCV001593300 likely pathogenic 16p11.2 deletion syndrome 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV001391677 SCV001593301 pathogenic Anal atresia, hypospadias, and penoscrotal inversion 2021-05-13 criteria provided, single submitter clinical testing
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University 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,National Human Genome Research Institute 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,National Human Genome Research Institute RCV001420681 SCV001623012 pathogenic Tyrosinase-positive oculocutaneous albinism 2021-02-01 criteria provided, single submitter research
Mayo Clinic Laboratories, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic RCV001449858 SCV001653255 uncertain significance not provided 2019-06-14 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001449859 SCV001653256 uncertain significance not provided 2021-03-24 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic RCV001449867 SCV001653264 uncertain significance not provided 2020-10-20 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic 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, Mayo Clinic RCV001449869 SCV001653266 uncertain significance not provided 2020-04-22 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001449870 SCV001653267 uncertain significance not provided 2021-01-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001449871 SCV001653268 uncertain significance not provided 2021-01-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001449872 SCV001653269 uncertain significance not provided 2020-10-15 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic RCV001449878 SCV001653275 uncertain significance not provided 2020-04-30 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic 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, Mayo Clinic 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, Mayo Clinic 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.
GeneDx RCV001527755 SCV001738886 benign not provided 2018-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001527805 SCV001738942 likely benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001527809 SCV001738946 likely benign not provided 2020-01-28 criteria provided, single submitter clinical testing
GeneDx RCV001527827 SCV001738965 benign not provided 2019-04-07 criteria provided, single submitter clinical testing
GeneDx RCV001527829 SCV001738967 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001527873 SCV001739016 benign not provided 2019-09-02 criteria provided, single submitter clinical testing
GeneDx RCV001527882 SCV001739025 benign not provided 2019-05-17 criteria provided, single submitter clinical testing
GeneDx RCV001527963 SCV001739114 benign not provided 2018-11-11 criteria provided, single submitter clinical testing
GeneDx RCV001528058 SCV001739219 likely benign not provided 2019-05-15 criteria provided, single submitter clinical testing
GeneDx RCV001528065 SCV001739227 benign not provided 2021-05-14 criteria provided, single submitter clinical testing
GeneDx RCV001530544 SCV001745417 benign not provided 2021-05-13 criteria provided, single submitter clinical testing
GeneDx RCV001530565 SCV001745442 benign not provided 2021-05-30 criteria provided, single submitter clinical testing
GeneDx RCV001530579 SCV001745457 benign not provided 2021-04-05 criteria provided, single submitter clinical testing
GeneDx RCV001530581 SCV001745459 benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001530609 SCV001745492 likely benign not provided 2020-05-18 criteria provided, single submitter clinical testing
GeneDx RCV001530620 SCV001745504 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001530625 SCV001745511 likely benign not provided 2019-01-20 criteria provided, single submitter clinical testing
GeneDx RCV001530740 SCV001745637 likely benign not provided 2019-09-02 criteria provided, single submitter clinical testing
GeneDx RCV001530795 SCV001745693 benign not provided 2018-07-26 criteria provided, single submitter clinical testing
GeneDx RCV001530806 SCV001745706 benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001530920 SCV001745832 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001531296 SCV001746326 likely benign not provided 2021-05-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001531653 SCV001746886 uncertain significance not provided 2021-02-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001531665 SCV001746904 likely benign not provided 2021-05-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001532159 SCV001747588 uncertain significance not provided 2021-05-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001532567 SCV001748187 likely benign not provided 2021-03-01 criteria provided, single submitter clinical testing
GeneDx RCV001533796 SCV001750657 benign not provided 2021-05-11 criteria provided, single submitter clinical testing
GeneDx RCV001533980 SCV001750863 benign not provided 2021-05-11 criteria provided, single submitter clinical testing
GeneDx RCV001533993 SCV001750878 benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001534023 SCV001750911 likely benign not provided 2018-07-17 criteria provided, single submitter clinical testing
GeneDx RCV001534169 SCV001751072 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001534191 SCV001751095 benign not provided 2019-01-10 criteria provided, single submitter clinical testing
GeneDx RCV001534262 SCV001751173 benign not provided 2021-05-22 criteria provided, single submitter clinical testing
GeneDx RCV001534283 SCV001751199 likely benign not provided 2019-08-13 criteria provided, single submitter clinical testing
GeneDx RCV001534295 SCV001751212 benign not provided 2018-11-11 criteria provided, single submitter clinical testing
GeneDx RCV001534319 SCV001751239 benign not provided 2019-02-28 criteria provided, single submitter clinical testing
GeneDx RCV001534360 SCV001751283 benign not provided 2018-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001534429 SCV001751358 benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001534530 SCV001751470 benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001534549 SCV001751490 benign not provided 2021-05-17 criteria provided, single submitter clinical testing
GeneDx RCV001534569 SCV001751512 likely benign not provided 2018-09-07 criteria provided, single submitter clinical testing
GeneDx RCV001534647 SCV001751580 likely benign not provided 2019-01-02 criteria provided, single submitter clinical testing
GeneDx RCV001534696 SCV001751638 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001534700 SCV001751642 benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001534728 SCV001751671 benign not provided 2021-05-14 criteria provided, single submitter clinical testing
GeneDx RCV001534737 SCV001751680 likely benign not provided 2019-08-24 criteria provided, single submitter clinical testing
GeneDx RCV001534794 SCV001751756 likely benign not provided 2019-04-29 criteria provided, single submitter clinical testing
GeneDx RCV001534905 SCV001751873 benign not provided 2019-10-28 criteria provided, single submitter clinical testing
GeneDx RCV001534935 SCV001751905 benign not provided 2018-11-16 criteria provided, single submitter clinical testing
GeneDx RCV001534943 SCV001751913 benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001535046 SCV001752024 likely benign not provided 2019-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001535119 SCV001752106 benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001535123 SCV001752110 likely benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001535151 SCV001752141 benign not provided 2020-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001535157 SCV001752147 benign not provided 2018-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001535237 SCV001752232 benign not provided 2019-01-10 criteria provided, single submitter clinical testing
GeneDx RCV001535241 SCV001752238 benign not provided 2019-08-09 criteria provided, single submitter clinical testing
GeneDx RCV001535255 SCV001752253 likely benign not provided 2019-08-06 criteria provided, single submitter clinical testing
GeneDx RCV001535272 SCV001752270 likely benign not provided 2019-03-25 criteria provided, single submitter clinical testing
GeneDx RCV001535300 SCV001752304 benign not provided 2021-05-10 criteria provided, single submitter clinical testing
GeneDx RCV001536184 SCV001752906 benign not provided 2021-05-11 criteria provided, single submitter clinical testing
GeneDx RCV001536186 SCV001752908 benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001536239 SCV001752968 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001536371 SCV001753121 benign not provided 2021-05-10 criteria provided, single submitter clinical testing
GeneDx RCV001536394 SCV001753145 benign not provided 2019-11-14 criteria provided, single submitter clinical testing
GeneDx RCV001536480 SCV001753244 benign not provided 2021-05-19 criteria provided, single submitter clinical testing
GeneDx RCV001536553 SCV001753328 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001536556 SCV001753331 benign not provided 2018-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001536567 SCV001753345 benign not provided 2018-12-22 criteria provided, single submitter clinical testing
GeneDx RCV001536600 SCV001753380 benign not provided 2019-09-09 criteria provided, single submitter clinical testing
GeneDx RCV001536606 SCV001753386 benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001536681 SCV001753476 benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001536719 SCV001753521 benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001536726 SCV001753529 benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001536784 SCV001753592 benign not provided 2018-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001536823 SCV001753633 benign not provided 2018-12-21 criteria provided, single submitter clinical testing
GeneDx RCV001536829 SCV001753639 benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001536870 SCV001753681 likely benign not provided 2020-05-25 criteria provided, single submitter clinical testing
GeneDx RCV001536875 SCV001753687 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001536881 SCV001753695 benign not provided 2018-10-16 criteria provided, single submitter clinical testing
GeneDx RCV001536910 SCV001753726 benign not provided 2021-05-21 criteria provided, single submitter clinical testing
GeneDx RCV001536936 SCV001753752 benign not provided 2018-09-18 criteria provided, single submitter clinical testing
GeneDx RCV001536937 SCV001753754 benign not provided 2018-07-17 criteria provided, single submitter clinical testing
GeneDx RCV001536995 SCV001753817 benign not provided 2021-05-15 criteria provided, single submitter clinical testing
GeneDx RCV001537041 SCV001753867 benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001537123 SCV001753957 benign not provided 2019-01-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29588580)
GeneDx RCV001537142 SCV001753983 benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001537207 SCV001754061 benign not provided 2018-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001537211 SCV001754065 benign not provided 2019-08-13 criteria provided, single submitter clinical testing
GeneDx RCV001537287 SCV001754152 benign not provided 2018-08-09 criteria provided, single submitter clinical testing
GeneDx RCV001537296 SCV001754162 benign not provided 2018-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001537309 SCV001754178 benign not provided 2021-05-14 criteria provided, single submitter clinical testing
GeneDx RCV001537402 SCV001754281 likely benign not provided 2018-10-02 criteria provided, single submitter clinical testing
GeneDx RCV001537408 SCV001754291 benign not provided 2021-06-20 criteria provided, single submitter clinical testing
GeneDx RCV001537427 SCV001754311 benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001537456 SCV001754341 benign not provided 2018-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001537480 SCV001754367 benign not provided 2021-05-10 criteria provided, single submitter clinical testing
GeneDx RCV001537499 SCV001754386 benign not provided 2019-08-06 criteria provided, single submitter clinical testing
GeneDx RCV001537513 SCV001754400 benign not provided 2019-11-06 criteria provided, single submitter clinical testing
GeneDx RCV001537590 SCV001754489 likely benign not provided 2019-11-13 criteria provided, single submitter clinical testing
GeneDx RCV001537619 SCV001754518 benign not provided 2019-02-21 criteria provided, single submitter clinical testing
GeneDx RCV001537625 SCV001754526 benign not provided 2021-06-18 criteria provided, single submitter clinical testing
GeneDx RCV001537626 SCV001754527 likely benign not provided 2019-08-31 criteria provided, single submitter clinical testing
GeneDx RCV001538087 SCV001755693 benign not provided 2018-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001538119 SCV001755727 likely benign not provided 2018-08-03 criteria provided, single submitter clinical testing
GeneDx RCV001538189 SCV001755803 likely benign not provided 2019-10-20 criteria provided, single submitter clinical testing
GeneDx RCV001538205 SCV001755820 benign not provided 2021-06-21 criteria provided, single submitter clinical testing
GeneDx RCV001538236 SCV001755858 benign not provided 2018-07-26 criteria provided, single submitter clinical testing
GeneDx RCV001538270 SCV001755897 benign not provided 2021-05-16 criteria provided, single submitter clinical testing
GeneDx RCV001538271 SCV001755898 benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001538320 SCV001755953 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001538344 SCV001755983 likely benign not provided 2018-10-21 criteria provided, single submitter clinical testing
GeneDx RCV001538355 SCV001755994 benign not provided 2018-09-23 criteria provided, single submitter clinical testing
GeneDx RCV001538394 SCV001756040 benign not provided 2021-05-10 criteria provided, single submitter clinical testing
GeneDx RCV001538492 SCV001756148 benign not provided 2018-07-17 criteria provided, single submitter clinical testing
GeneDx RCV001538499 SCV001756159 likely benign not provided 2020-10-20 criteria provided, single submitter clinical testing
GeneDx RCV001538504 SCV001756167 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001538520 SCV001756184 benign not provided 2021-05-14 criteria provided, single submitter clinical testing
GeneDx RCV001538595 SCV001756269 benign not provided 2018-08-17 criteria provided, single submitter clinical testing
GeneDx RCV001538630 SCV001756308 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001538688 SCV001756370 benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001538722 SCV001756407 benign not provided 2021-06-20 criteria provided, single submitter clinical testing
GeneDx RCV001538745 SCV001756436 benign not provided 2021-05-11 criteria provided, single submitter clinical testing
GeneDx RCV001538881 SCV001756596 benign not provided 2018-07-03 criteria provided, single submitter clinical testing
GeneDx RCV001538917 SCV001756636 benign not provided 2018-12-22 criteria provided, single submitter clinical testing
GeneDx RCV001538923 SCV001756642 benign not provided 2020-12-01 criteria provided, single submitter clinical testing
GeneDx RCV001538963 SCV001756685 benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001538978 SCV001756701 benign not provided 2018-08-16 criteria provided, single submitter clinical testing
GeneDx RCV001539000 SCV001756727 benign not provided 2019-03-01 criteria provided, single submitter clinical testing
GeneDx RCV001539002 SCV001756729 likely benign not provided 2018-07-30 criteria provided, single submitter clinical testing
GeneDx RCV001539044 SCV001756776 benign not provided 2021-06-18 criteria provided, single submitter clinical testing
GeneDx RCV001539047 SCV001756779 benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001539082 SCV001756819 benign not provided 2020-08-02 criteria provided, single submitter clinical testing
GeneDx RCV001539134 SCV001756878 benign not provided 2021-05-28 criteria provided, single submitter clinical testing
GeneDx RCV001539181 SCV001756925 likely benign not provided 2018-07-26 criteria provided, single submitter clinical testing
GeneDx RCV001539239 SCV001756986 benign not provided 2018-06-16 criteria provided, single submitter clinical testing
GeneDx RCV001539328 SCV001757087 benign not provided 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV001539340 SCV001757102 benign not provided 2019-06-21 criteria provided, single submitter clinical testing
GeneDx RCV001539382 SCV001757152 benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001539398 SCV001757172 benign not provided 2018-07-17 criteria provided, single submitter clinical testing
GeneDx RCV001539443 SCV001757225 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001539489 SCV001757275 benign not provided 2019-08-18 criteria provided, single submitter clinical testing
GeneDx RCV001539490 SCV001757276 benign not provided 2021-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001539506 SCV001757293 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001539591 SCV001757379 benign not provided 2019-08-26 criteria provided, single submitter clinical testing
GeneDx RCV001539692 SCV001757492 benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001539716 SCV001757519 likely benign not provided 2019-01-31 criteria provided, single submitter clinical testing
GeneDx RCV001539837 SCV001757656 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
GeneDx RCV001539896 SCV001757720 benign not provided 2021-04-25 criteria provided, single submitter clinical testing
GeneDx RCV001539918 SCV001757743 benign not provided 2021-05-17 criteria provided, single submitter clinical testing
GeneDx RCV001539951 SCV001757779 benign not provided 2018-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001539988 SCV001757818 benign not provided 2018-07-03 criteria provided, single submitter clinical testing
GeneDx RCV001540039 SCV001757875 likely benign not provided 2019-01-13 criteria provided, single submitter clinical testing
GeneDx RCV001540129 SCV001757975 benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001540155 SCV001758007 benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001540181 SCV001758036 benign not provided 2018-10-17 criteria provided, single submitter clinical testing
GeneDx RCV001540294 SCV001758166 benign not provided 2018-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001540477 SCV001758368 benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001540538 SCV001758432 benign not provided 2021-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001540549 SCV001758444 likely benign not provided 2018-09-26 criteria provided, single submitter clinical testing
GeneDx RCV001540617 SCV001758519 benign not provided 2018-06-18 criteria provided, single submitter clinical testing
GeneDx RCV001540772 SCV001758693 benign not provided 2021-06-18 criteria provided, single submitter clinical testing
GeneDx RCV001540860 SCV001758788 benign not provided 2021-05-11 criteria provided, single submitter clinical testing
GeneDx RCV001541076 SCV001759031 likely benign not provided 2019-06-07 criteria provided, single submitter clinical testing
GeneDx RCV001541088 SCV001759043 benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001541090 SCV001759046 benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001541203 SCV001759172 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
GeneDx RCV001541222 SCV001759194 benign not provided 2021-05-28 criteria provided, single submitter clinical testing
GeneDx RCV001541230 SCV001759204 benign not provided 2021-05-10 criteria provided, single submitter clinical testing
GeneDx RCV001541328 SCV001759308 benign not provided 2018-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001541387 SCV001759380 likely benign not provided 2018-11-16 criteria provided, single submitter clinical testing
GeneDx RCV001541412 SCV001759409 benign not provided 2018-08-30 criteria provided, single submitter clinical testing
GeneDx RCV001541551 SCV001759565 likely benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001541563 SCV001759580 likely benign not provided 2019-08-20 criteria provided, single submitter clinical testing
GeneDx RCV001541604 SCV001759623 benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001541634 SCV001759656 benign not provided 2021-05-24 criteria provided, single submitter clinical testing
GeneDx RCV001541652 SCV001759677 benign not provided 2021-06-18 criteria provided, single submitter clinical testing
GeneDx RCV001541671 SCV001759697 benign not provided 2018-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001541697 SCV001759725 benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001541849 SCV001759888 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001541855 SCV001759896 likely benign not provided 2020-03-11 criteria provided, single submitter clinical testing
GeneDx RCV001541875 SCV001759921 benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001541888 SCV001759955 benign not provided 2021-06-18 criteria provided, single submitter clinical testing
Molecular Pathology Research Laboratory,SA Pathology 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,SA Pathology 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,SA Pathology 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,SA Pathology 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,SA Pathology 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,SA Pathology 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,SA Pathology 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, University Hospital Tübingen RCV001543588 SCV001762260 likely pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
GeneDx RCV001544701 SCV001763879 likely benign not provided 2019-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001544765 SCV001763961 likely benign not provided 2018-09-16 criteria provided, single submitter clinical testing
GeneDx RCV001544792 SCV001763991 likely benign not provided 2019-06-15 criteria provided, single submitter clinical testing
GeneDx RCV001544915 SCV001764139 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001544930 SCV001764158 likely benign not provided 2018-12-12 criteria provided, single submitter clinical testing
GeneDx RCV001544952 SCV001764183 likely benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001544961 SCV001764193 likely benign not provided 2019-08-18 criteria provided, single submitter clinical testing
GeneDx RCV001544965 SCV001764197 likely benign not provided 2021-01-12 criteria provided, single submitter clinical testing
GeneDx RCV001545111 SCV001764375 likely benign not provided 2019-09-13 criteria provided, single submitter clinical testing
GeneDx RCV001545124 SCV001764393 likely benign not provided 2018-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001545174 SCV001764452 likely benign not provided 2018-07-28 criteria provided, single submitter clinical testing
GeneDx RCV001545245 SCV001764537 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001545287 SCV001764593 likely benign not provided 2019-09-29 criteria provided, single submitter clinical testing
GeneDx RCV001545302 SCV001764612 likely benign not provided 2018-10-24 criteria provided, single submitter clinical testing
GeneDx RCV001545313 SCV001764624 likely benign not provided 2018-09-18 criteria provided, single submitter clinical testing
GeneDx RCV001545319 SCV001764633 likely benign not provided 2019-12-29 criteria provided, single submitter clinical testing
GeneDx RCV001545411 SCV001764737 likely benign not provided 2019-03-29 criteria provided, single submitter clinical testing
GeneDx RCV001545500 SCV001764842 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV001545649 SCV001765025 likely benign not provided 2019-06-17 criteria provided, single submitter clinical testing
GeneDx RCV001545659 SCV001765036 likely benign not provided 2018-08-14 criteria provided, single submitter clinical testing
GeneDx RCV001545667 SCV001765045 likely benign not provided 2018-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001545923 SCV001765345 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001546017 SCV001765457 likely benign not provided 2019-08-21 criteria provided, single submitter clinical testing
GeneDx RCV001546105 SCV001765561 likely benign not provided 2019-02-24 criteria provided, single submitter clinical testing
GeneDx RCV001546195 SCV001765671 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001546200 SCV001765678 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001546330 SCV001765826 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001546341 SCV001765838 likely benign not provided 2019-08-21 criteria provided, single submitter clinical testing
GeneDx RCV001546401 SCV001765911 likely benign not provided 2019-09-29 criteria provided, single submitter clinical testing
GeneDx RCV001546440 SCV001765958 likely benign not provided 2019-08-16 criteria provided, single submitter clinical testing
GeneDx RCV001546445 SCV001765965 likely benign not provided 2019-09-06 criteria provided, single submitter clinical testing
GeneDx RCV001546488 SCV001766015 likely benign not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV001546545 SCV001766077 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001546549 SCV001766081 likely benign not provided 2018-08-07 criteria provided, single submitter clinical testing
GeneDx RCV001546650 SCV001766202 likely benign not provided 2018-06-28 criteria provided, single submitter clinical testing
GeneDx RCV001546725 SCV001766296 likely benign not provided 2018-08-03 criteria provided, single submitter clinical testing
GeneDx RCV001546739 SCV001766314 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001546757 SCV001766335 likely benign not provided 2018-10-17 criteria provided, single submitter clinical testing
GeneDx RCV001546772 SCV001766352 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001546798 SCV001766382 likely benign not provided 2018-11-16 criteria provided, single submitter clinical testing
GeneDx RCV001546864 SCV001766461 likely benign not provided 2018-10-02 criteria provided, single submitter clinical testing
GeneDx RCV001546871 SCV001766468 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001546977 SCV001766593 likely benign not provided 2018-08-03 criteria provided, single submitter clinical testing
GeneDx RCV001547035 SCV001766654 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001547063 SCV001766685 likely benign not provided 2018-08-28 criteria provided, single submitter clinical testing
GeneDx RCV001547121 SCV001766751 likely benign not provided 2019-11-04 criteria provided, single submitter clinical testing
GeneDx RCV001547191 SCV001766839 likely benign not provided 2018-06-22 criteria provided, single submitter clinical testing
GeneDx RCV001547206 SCV001766856 likely benign not provided 2019-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001547274 SCV001766938 likely benign not provided 2018-11-16 criteria provided, single submitter clinical testing
GeneDx RCV001547302 SCV001766971 likely benign not provided 2018-08-07 criteria provided, single submitter clinical testing
GeneDx RCV001547322 SCV001766994 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001547352 SCV001767037 likely benign not provided 2018-09-07 criteria provided, single submitter clinical testing
GeneDx RCV001547363 SCV001767050 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001547368 SCV001767056 likely benign not provided 2019-08-13 criteria provided, single submitter clinical testing
GeneDx RCV001547390 SCV001767083 likely benign not provided 2019-05-20 criteria provided, single submitter clinical testing
GeneDx RCV001547525 SCV001767257 likely benign not provided 2018-07-11 criteria provided, single submitter clinical testing
GeneDx RCV001547622 SCV001767373 likely benign not provided 2018-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001547629 SCV001767382 likely benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001547667 SCV001767429 likely benign not provided 2019-10-30 criteria provided, single submitter clinical testing
GeneDx RCV001547860 SCV001767660 likely benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001547874 SCV001767676 likely benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx 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
GeneDx RCV001547879 SCV001767685 likely benign not provided 2020-01-10 criteria provided, single submitter clinical testing
GeneDx RCV001548003 SCV001767845 likely benign not provided 2018-12-23 criteria provided, single submitter clinical testing
GeneDx RCV001548187 SCV001768054 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001548345 SCV001768240 likely benign not provided 2018-10-27 criteria provided, single submitter clinical testing
GeneDx RCV001548381 SCV001768281 likely benign not provided 2019-11-14 criteria provided, single submitter clinical testing
GeneDx RCV001548386 SCV001768288 likely benign not provided 2018-09-26 criteria provided, single submitter clinical testing
GeneDx RCV001548425 SCV001768332 likely benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001549312 SCV001769437 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001549347 SCV001769481 likely benign not provided 2020-04-06 criteria provided, single submitter clinical testing
GeneDx RCV001549514 SCV001769679 likely benign not provided 2019-02-11 criteria provided, single submitter clinical testing
GeneDx RCV001549542 SCV001769719 likely benign not provided 2018-06-21 criteria provided, single submitter clinical testing
GeneDx RCV001549556 SCV001769735 likely benign not provided 2020-04-02 criteria provided, single submitter clinical testing
GeneDx RCV001549643 SCV001769828 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001549681 SCV001769875 likely benign not provided 2019-05-19 criteria provided, single submitter clinical testing
GeneDx RCV001549798 SCV001770014 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001549842 SCV001770070 likely benign not provided 2018-12-05 criteria provided, single submitter clinical testing
GeneDx RCV001549854 SCV001770082 likely benign not provided 2019-01-20 criteria provided, single submitter clinical testing
GeneDx RCV001549970 SCV001770217 likely benign not provided 2019-12-10 criteria provided, single submitter clinical testing
GeneDx RCV001550034 SCV001770302 likely benign not provided 2020-08-28 criteria provided, single submitter clinical testing
GeneDx RCV001550037 SCV001770305 likely benign not provided 2019-08-18 criteria provided, single submitter clinical testing
GeneDx RCV001550060 SCV001770331 likely benign not provided 2018-12-12 criteria provided, single submitter clinical testing
GeneDx RCV001550099 SCV001770379 likely benign not provided 2019-01-28 criteria provided, single submitter clinical testing
GeneDx RCV001550190 SCV001770482 likely benign not provided 2018-10-21 criteria provided, single submitter clinical testing
GeneDx RCV001550257 SCV001770557 likely benign not provided 2019-08-18 criteria provided, single submitter clinical testing
GeneDx RCV001550316 SCV001770626 likely benign not provided 2020-05-30 criteria provided, single submitter clinical testing
GeneDx RCV001550375 SCV001770690 likely benign not provided 2018-08-17 criteria provided, single submitter clinical testing
GeneDx RCV001550540 SCV001770879 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV001550682 SCV001771052 likely benign not provided 2020-03-07 criteria provided, single submitter clinical testing
GeneDx RCV001550688 SCV001771061 likely benign not provided 2018-08-12 criteria provided, single submitter clinical testing
GeneDx RCV001550719 SCV001771097 likely benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001550733 SCV001771113 likely benign not provided 2018-07-02 criteria provided, single submitter clinical testing
GeneDx RCV001550756 SCV001771140 likely benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001550780 SCV001771167 likely benign not provided 2019-08-20 criteria provided, single submitter clinical testing
GeneDx RCV001550805 SCV001771195 likely benign not provided 2019-10-21 criteria provided, single submitter clinical testing
GeneDx RCV001550810 SCV001771200 likely benign not provided 2018-09-26 criteria provided, single submitter clinical testing
GeneDx RCV001550840 SCV001771235 likely benign not provided 2018-08-30 criteria provided, single submitter clinical testing
GeneDx RCV001550873 SCV001771272 likely benign not provided 2020-03-14 criteria provided, single submitter clinical testing
GeneDx RCV001550941 SCV001771349 likely benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001551061 SCV001771486 likely benign not provided 2019-02-24 criteria provided, single submitter clinical testing
GeneDx 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)
GeneDx RCV001551124 SCV001771560 likely benign not provided 2019-05-20 criteria provided, single submitter clinical testing
GeneDx RCV001551176 SCV001771629 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001551177 SCV001771630 likely benign not provided 2018-09-27 criteria provided, single submitter clinical testing
GeneDx RCV001551248 SCV001771715 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001551302 SCV001771781 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001551351 SCV001771837 likely benign not provided 2018-08-11 criteria provided, single submitter clinical testing
GeneDx RCV001551364 SCV001771853 likely benign not provided 2019-09-20 criteria provided, single submitter clinical testing
GeneDx RCV001551403 SCV001771907 likely benign not provided 2019-08-15 criteria provided, single submitter clinical testing
GeneDx RCV001551489 SCV001772010 likely benign not provided 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001551498 SCV001772020 likely benign not provided 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001551531 SCV001772055 likely benign not provided 2019-08-06 criteria provided, single submitter clinical testing
GeneDx RCV001551571 SCV001772102 likely benign not provided 2019-08-07 criteria provided, single submitter clinical testing
GeneDx RCV001551578 SCV001772112 likely benign not provided 2018-08-14 criteria provided, single submitter clinical testing
GeneDx RCV001551620 SCV001772161 likely benign not provided 2019-05-03 criteria provided, single submitter clinical testing
GeneDx RCV001551679 SCV001772238 likely benign not provided 2018-07-28 criteria provided, single submitter clinical testing
GeneDx RCV001551766 SCV001772339 likely benign not provided 2019-04-20 criteria provided, single submitter clinical testing
GeneDx RCV001551881 SCV001772478 likely benign not provided 2019-10-07 criteria provided, single submitter clinical testing
GeneDx RCV001551940 SCV001772548 likely benign not provided 2018-07-29 criteria provided, single submitter clinical testing
GeneDx RCV001552020 SCV001772634 likely benign not provided 2018-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001552046 SCV001772662 likely benign not provided 2018-12-22 criteria provided, single submitter clinical testing
GeneDx RCV001552178 SCV001772825 likely benign not provided 2019-08-26 criteria provided, single submitter clinical testing
GeneDx RCV001552187 SCV001772835 likely benign not provided 2019-12-10 criteria provided, single submitter clinical testing
GeneDx RCV001552207 SCV001772857 likely benign not provided 2018-06-28 criteria provided, single submitter clinical testing
GeneDx RCV001552271 SCV001772929 likely benign not provided 2019-11-02 criteria provided, single submitter clinical testing
GeneDx RCV001552359 SCV001773031 likely benign not provided 2019-06-12 criteria provided, single submitter clinical testing
GeneDx RCV001552397 SCV001773075 likely benign not provided 2020-03-15 criteria provided, single submitter clinical testing
GeneDx RCV001552417 SCV001773099 likely benign not provided 2019-10-24 criteria provided, single submitter clinical testing
GeneDx RCV001552505 SCV001773203 likely benign not provided 2018-08-07 criteria provided, single submitter clinical testing
GeneDx RCV001552509 SCV001773208 likely benign not provided 2018-08-15 criteria provided, single submitter clinical testing
GeneDx RCV001552559 SCV001773265 likely benign not provided 2020-02-13 criteria provided, single submitter clinical testing
GeneDx RCV001552659 SCV001773387 likely benign not provided 2019-11-13 criteria provided, single submitter clinical testing
GeneDx RCV001552762 SCV001773512 likely benign not provided 2019-04-16 criteria provided, single submitter clinical testing
GeneDx RCV001552823 SCV001773587 likely benign not provided 2019-12-24 criteria provided, single submitter clinical testing
GeneDx RCV001552967 SCV001773751 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001552993 SCV001773784 likely benign not provided 2018-08-31 criteria provided, single submitter clinical testing
GeneDx RCV001553026 SCV001773821 likely benign not provided 2020-08-04 criteria provided, single submitter clinical testing
GeneDx RCV001553161 SCV001773978 likely benign not provided 2018-10-05 criteria provided, single submitter clinical testing
GeneDx RCV001553371 SCV001774230 likely benign not provided 2021-01-12 criteria provided, single submitter clinical testing
GeneDx RCV001553413 SCV001774275 likely benign not provided 2018-09-18 criteria provided, single submitter clinical testing
GeneDx RCV001553462 SCV001774335 likely benign not provided 2019-08-24 criteria provided, single submitter clinical testing
GeneDx RCV001553506 SCV001774386 likely benign not provided 2019-04-12 criteria provided, single submitter clinical testing
GeneDx RCV001553531 SCV001774416 likely benign not provided 2019-10-13 criteria provided, single submitter clinical testing
GeneDx RCV001554962 SCV001776303 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001555015 SCV001776361 likely benign not provided 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001555034 SCV001776383 likely benign not provided 2019-08-08 criteria provided, single submitter clinical testing
GeneDx RCV001555060 SCV001776413 likely benign not provided 2018-11-08 criteria provided, single submitter clinical testing
GeneDx RCV001555063 SCV001776417 likely benign not provided 2019-08-13 criteria provided, single submitter clinical testing
GeneDx RCV001555106 SCV001776460 likely benign not provided 2018-08-17 criteria provided, single submitter clinical testing
GeneDx RCV001555164 SCV001776531 likely benign not provided 2018-10-05 criteria provided, single submitter clinical testing
GeneDx RCV001555173 SCV001776542 likely benign not provided 2020-01-23 criteria provided, single submitter clinical testing
GeneDx RCV001555183 SCV001776554 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001555231 SCV001776611 likely benign not provided 2018-06-30 criteria provided, single submitter clinical testing
GeneDx RCV001555310 SCV001776703 likely benign not provided 2018-08-14 criteria provided, single submitter clinical testing
GeneDx RCV001555360 SCV001776768 likely benign not provided 2019-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001555513 SCV001776949 likely benign not provided 2018-09-22 criteria provided, single submitter clinical testing
GeneDx RCV001555519 SCV001776957 likely benign not provided 2018-07-11 criteria provided, single submitter clinical testing
GeneDx RCV001555633 SCV001777081 likely benign not provided 2018-11-08 criteria provided, single submitter clinical testing
GeneDx RCV001555638 SCV001777086 likely benign not provided 2018-10-28 criteria provided, single submitter clinical testing
GeneDx RCV001555643 SCV001777092 likely benign not provided 2018-08-14 criteria provided, single submitter clinical testing
GeneDx RCV001555674 SCV001777126 likely benign not provided 2018-08-03 criteria provided, single submitter clinical testing
GeneDx RCV001555757 SCV001777220 likely benign not provided 2018-08-17 criteria provided, single submitter clinical testing
GeneDx RCV001555759 SCV001777222 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx 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)
GeneDx RCV001555801 SCV001777270 likely benign not provided 2019-04-12 criteria provided, single submitter clinical testing
GeneDx RCV001555836 SCV001777312 likely benign not provided 2019-09-29 criteria provided, single submitter clinical testing
GeneDx RCV001555865 SCV001777350 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001555898 SCV001777388 likely benign not provided 2018-10-24 criteria provided, single submitter clinical testing
GeneDx RCV001555929 SCV001777422 likely benign not provided 2019-08-18 criteria provided, single submitter clinical testing
GeneDx RCV001556044 SCV001777556 likely benign not provided 2019-04-12 criteria provided, single submitter clinical testing
GeneDx RCV001556161 SCV001777691 likely benign not provided 2018-10-17 criteria provided, single submitter clinical testing
GeneDx RCV001556195 SCV001777730 likely benign not provided 2019-09-26 criteria provided, single submitter clinical testing
GeneDx RCV001556299 SCV001777857 likely benign not provided 2018-10-09 criteria provided, single submitter clinical testing
GeneDx RCV001556303 SCV001777861 likely benign not provided 2018-10-28 criteria provided, single submitter clinical testing
GeneDx RCV001556437 SCV001778019 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001556617 SCV001778230 likely benign not provided 2018-07-14 criteria provided, single submitter clinical testing
GeneDx 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
GeneDx RCV001556691 SCV001778318 likely benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001556813 SCV001778460 likely benign not provided 2019-10-12 criteria provided, single submitter clinical testing
GeneDx RCV001556867 SCV001778523 likely benign not provided 2019-10-21 criteria provided, single submitter clinical testing
GeneDx RCV001556910 SCV001778575 likely benign not provided 2018-09-26 criteria provided, single submitter clinical testing
GeneDx RCV001557127 SCV001778831 likely benign not provided 2019-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001557246 SCV001778973 likely benign not provided 2019-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001557254 SCV001778982 likely benign not provided 2019-02-05 criteria provided, single submitter clinical testing
GeneDx RCV001557275 SCV001779006 likely benign not provided 2019-10-28 criteria provided, single submitter clinical testing
GeneDx RCV001557331 SCV001779078 likely benign not provided 2018-11-10 criteria provided, single submitter clinical testing
GeneDx RCV001557374 SCV001779127 likely benign not provided 2018-12-23 criteria provided, single submitter clinical testing
GeneDx RCV001557494 SCV001779265 likely benign not provided 2019-03-21 criteria provided, single submitter clinical testing
GeneDx RCV001557621 SCV001779413 likely benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001557687 SCV001779494 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001557996 SCV001779857 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001558046 SCV001779917 likely benign not provided 2019-06-28 criteria provided, single submitter clinical testing
GeneDx RCV001558158 SCV001780047 likely benign not provided 2019-07-13 criteria provided, single submitter clinical testing
GeneDx RCV001558162 SCV001780051 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001558168 SCV001780058 likely benign not provided 2019-02-14 criteria provided, single submitter clinical testing
GeneDx RCV001558224 SCV001780125 likely benign not provided 2019-06-15 criteria provided, single submitter clinical testing
GeneDx RCV001558289 SCV001780203 likely benign not provided 2019-09-23 criteria provided, single submitter clinical testing
GeneDx RCV001558524 SCV001780489 likely benign not provided 2020-01-05 criteria provided, single submitter clinical testing
GeneDx RCV001558571 SCV001780549 likely benign not provided 2019-01-02 criteria provided, single submitter clinical testing
GeneDx RCV001558610 SCV001780598 likely benign not provided 2020-04-01 criteria provided, single submitter clinical testing
GeneDx RCV001558628 SCV001780619 likely benign not provided 2018-08-26 criteria provided, single submitter clinical testing
GeneDx RCV001558670 SCV001780667 likely benign not provided 2019-11-13 criteria provided, single submitter clinical testing
GeneDx RCV001558672 SCV001780669 likely benign not provided 2019-05-06 criteria provided, single submitter clinical testing
GeneDx RCV001558682 SCV001780681 likely benign not provided 2020-01-20 criteria provided, single submitter clinical testing
GeneDx RCV001558775 SCV001780791 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001558814 SCV001780835 likely benign not provided 2020-12-30 criteria provided, single submitter clinical testing
GeneDx RCV001558822 SCV001780845 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001558867 SCV001780898 likely benign not provided 2019-06-12 criteria provided, single submitter clinical testing
GeneDx RCV001558910 SCV001780952 likely benign not provided 2018-06-22 criteria provided, single submitter clinical testing
GeneDx RCV001558968 SCV001781016 likely benign not provided 2020-02-16 criteria provided, single submitter clinical testing
GeneDx RCV001559346 SCV001781560 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001559350 SCV001781564 likely benign not provided 2019-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001559360 SCV001781574 likely benign not provided 2020-04-24 criteria provided, single submitter clinical testing
GeneDx RCV001559420 SCV001781639 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001559499 SCV001781736 likely benign not provided 2019-03-06 criteria provided, single submitter clinical testing
GeneDx RCV001559524 SCV001781763 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV001559564 SCV001781817 likely benign not provided 2019-03-06 criteria provided, single submitter clinical testing
GeneDx RCV001559616 SCV001781886 likely benign not provided 2018-10-16 criteria provided, single submitter clinical testing
GeneDx RCV001559682 SCV001781966 likely benign not provided 2019-06-15 criteria provided, single submitter clinical testing
GeneDx RCV001559707 SCV001781997 likely benign not provided 2019-08-08 criteria provided, single submitter clinical testing
GeneDx RCV001559800 SCV001782099 likely benign not provided 2019-02-28 criteria provided, single submitter clinical testing
GeneDx RCV001559940 SCV001782266 likely benign not provided 2020-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001559957 SCV001782285 likely benign not provided 2019-04-07 criteria provided, single submitter clinical testing
GeneDx RCV001560006 SCV001782336 likely benign not provided 2018-08-17 criteria provided, single submitter clinical testing
GeneDx RCV001560058 SCV001782392 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001560098 SCV001782438 likely benign not provided 2018-10-17 criteria provided, single submitter clinical testing
GeneDx RCV001560177 SCV001782533 likely benign not provided 2018-08-03 criteria provided, single submitter clinical testing
GeneDx RCV001560315 SCV001782701 likely benign not provided 2018-11-11 criteria provided, single submitter clinical testing
GeneDx RCV001560319 SCV001782705 likely benign not provided 2019-08-10 criteria provided, single submitter clinical testing
GeneDx RCV001560365 SCV001782763 likely benign not provided 2020-02-13 criteria provided, single submitter clinical testing
GeneDx RCV001560425 SCV001782838 likely benign not provided 2018-07-08 criteria provided, single submitter clinical testing
GeneDx RCV001560464 SCV001782882 likely benign not provided 2018-07-21 criteria provided, single submitter clinical testing
GeneDx RCV001560544 SCV001782975 likely benign not provided 2020-08-20 criteria provided, single submitter clinical testing
GeneDx RCV001560574 SCV001783011 likely benign not provided 2018-08-07 criteria provided, single submitter clinical testing
GeneDx RCV001560622 SCV001783074 likely benign not provided 2019-06-12 criteria provided, single submitter clinical testing
GeneDx RCV001560694 SCV001783155 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001560704 SCV001783167 likely benign not provided 2019-04-14 criteria provided, single submitter clinical testing
GeneDx RCV001560728 SCV001783196 likely benign not provided 2018-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001560854 SCV001783345 likely benign not provided 2019-04-10 criteria provided, single submitter clinical testing
GeneDx RCV001560943 SCV001783451 likely benign not provided 2018-09-16 criteria provided, single submitter clinical testing
GeneDx RCV001560995 SCV001783511 likely benign not provided 2019-08-16 criteria provided, single submitter clinical testing
GeneDx RCV001561057 SCV001783584 likely benign not provided 2018-12-31 criteria provided, single submitter clinical testing
GeneDx RCV001561072 SCV001783603 likely benign not provided 2019-11-07 criteria provided, single submitter clinical testing
GeneDx RCV001561075 SCV001783607 likely benign not provided 2019-11-08 criteria provided, single submitter clinical testing
GeneDx RCV001561115 SCV001783652 likely benign not provided 2019-06-17 criteria provided, single submitter clinical testing
GeneDx RCV001561377 SCV001783975 likely benign not provided 2019-08-15 criteria provided, single submitter clinical testing
GeneDx RCV001561414 SCV001784017 likely benign not provided 2018-08-03 criteria provided, single submitter clinical testing
GeneDx RCV001561451 SCV001784060 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001561467 SCV001784077 likely benign not provided 2019-10-25 criteria provided, single submitter clinical testing
GeneDx RCV001561657 SCV001784295 likely benign not provided 2019-08-06 criteria provided, single submitter clinical testing
GeneDx RCV001561666 SCV001784306 likely benign not provided 2018-07-09 criteria provided, single submitter clinical testing
GeneDx RCV001561902 SCV001784588 likely benign not provided 2018-07-07 criteria provided, single submitter clinical testing
GeneDx RCV001561904 SCV001784591 likely benign not provided 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001561937 SCV001784627 likely benign not provided 2018-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001561979 SCV001784677 likely benign not provided 2020-07-27 criteria provided, single submitter clinical testing
GeneDx RCV001562195 SCV001784925 likely benign not provided 2019-11-13 criteria provided, single submitter clinical testing
GeneDx RCV001562241 SCV001784977 likely benign not provided 2019-01-25 criteria provided, single submitter clinical testing
GeneDx RCV001562378 SCV001785133 likely benign not provided 2019-12-29 criteria provided, single submitter clinical testing
GeneDx RCV001562409 SCV001785168 likely benign not provided 2020-09-11 criteria provided, single submitter clinical testing Identified in two unrelated families with a clinical diagnosis of MODY in published literature; however, each patient harbored a second HNF4A variant (Anuradha et al., 2011); This variant is associated with the following publications: (PMID: 23014256, 21062274)
GeneDx RCV001562479 SCV001785249 likely benign not provided 2019-11-29 criteria provided, single submitter clinical testing
GeneDx RCV001562518 SCV001785294 likely benign not provided 2018-08-09 criteria provided, single submitter clinical testing
GeneDx RCV001562702 SCV001785508 likely benign not provided 2019-10-02 criteria provided, single submitter clinical testing
GeneDx RCV001562755 SCV001785570 likely benign not provided 2018-08-12 criteria provided, single submitter clinical testing
GeneDx RCV001562873 SCV001785710 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001562887 SCV001785726 likely benign not provided 2019-11-22 criteria provided, single submitter clinical testing
GeneDx RCV001562888 SCV001785727 likely benign not provided 2020-11-03 criteria provided, single submitter clinical testing
GeneDx RCV001562903 SCV001785745 likely benign not provided 2020-12-05 criteria provided, single submitter clinical testing
GeneDx RCV001562914 SCV001785760 likely benign not provided 2018-10-24 criteria provided, single submitter clinical testing
GeneDx RCV001563075 SCV001785953 likely benign not provided 2019-04-24 criteria provided, single submitter clinical testing
GeneDx RCV001563095 SCV001785977 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV001563109 SCV001785993 likely benign not provided 2018-07-20 criteria provided, single submitter clinical testing
GeneDx RCV001563122 SCV001786007 likely benign not provided 2018-08-12 criteria provided, single submitter clinical testing
GeneDx RCV001563146 SCV001786035 likely benign not provided 2019-06-29 criteria provided, single submitter clinical testing
GeneDx RCV001563176 SCV001786067 likely benign not provided 2019-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001563258 SCV001786166 likely benign not provided 2018-07-21 criteria provided, single submitter clinical testing
GeneDx RCV001563288 SCV001786201 likely benign not provided 2019-08-16 criteria provided, single submitter clinical testing
GeneDx RCV001563361 SCV001786289 likely benign not provided 2018-10-02 criteria provided, single submitter clinical testing
GeneDx RCV001563485 SCV001786436 likely benign not provided 2018-09-16 criteria provided, single submitter clinical testing
GeneDx RCV001563525 SCV001786485 likely benign not provided 2020-07-19 criteria provided, single submitter clinical testing
GeneDx RCV001564121 SCV001787230 likely benign not provided 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001564173 SCV001787294 likely benign not provided 2018-09-22 criteria provided, single submitter clinical testing
GeneDx RCV001564239 SCV001787374 likely benign not provided 2019-01-29 criteria provided, single submitter clinical testing
GeneDx RCV001564288 SCV001787432 likely benign not provided 2018-12-24 criteria provided, single submitter clinical testing
GeneDx RCV001564315 SCV001787462 likely benign not provided 2019-10-16 criteria provided, single submitter clinical testing
GeneDx RCV001564332 SCV001787484 likely benign not provided 2018-10-01 criteria provided, single submitter clinical testing
GeneDx RCV001564409 SCV001787571 likely benign not provided 2019-03-03 criteria provided, single submitter clinical testing
GeneDx RCV001564455 SCV001787627 likely benign not provided 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV001564575 SCV001787760 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing
GeneDx RCV001564626 SCV001787820 likely benign not provided 2018-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001564696 SCV001787896 likely benign not provided 2018-07-26 criteria provided, single submitter clinical testing
GeneDx RCV001564711 SCV001787914 likely benign not provided 2019-04-24 criteria provided, single submitter clinical testing
GeneDx RCV001564732 SCV001787940 likely benign not provided 2018-09-07 criteria provided, single submitter clinical testing
GeneDx RCV001564868 SCV001788103 likely benign not provided 2018-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001565208 SCV001788513 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV001565424 SCV001788763 likely benign not provided 2019-04-24 criteria provided, single submitter clinical testing
GeneDx RCV001565506 SCV001788862 likely benign not provided 2019-01-13 criteria provided, single submitter clinical testing
GeneDx RCV001565569 SCV001788937 likely benign not provided 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001565594 SCV001788968 likely benign not provided 2019-08-26 criteria provided, single submitter clinical testing
GeneDx RCV001565603 SCV001788978 likely benign not provided 2019-08-21 criteria provided, single submitter clinical testing
GeneDx RCV001565678 SCV001789070 likely benign not provided 2018-12-17 criteria provided, single submitter clinical testing
GeneDx RCV001565810 SCV001789226 likely benign not provided 2019-09-15 criteria provided, single submitter clinical testing
GeneDx RCV001565913 SCV001789356 likely benign not provided 2018-06-23 criteria provided, single submitter clinical testing
GeneDx RCV001565928 SCV001789374 likely benign not provided 2018-07-21 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27625398)
GeneDx RCV001565938 SCV001789387 likely benign not provided 2020-03-31 criteria provided, single submitter clinical testing
GeneDx RCV001565961 SCV001789414