Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000082477 | SCV000054858 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000040989 | SCV000064680 | benign | not specified | 2017-10-12 | criteria provided, single submitter | clinical testing | p.Met33291Thr variant in exon 311 of TTN: This variant is not expected to have c linical significance because it has been identified in 0.9% (275/30782) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomAD.bro adinstitute.org; dbSNP rs72629793). ACMG/AMP Criteria applied: BA1(Richards 2015 ). |
Gene |
RCV000040989 | SCV000236912 | benign | not specified | 2016-08-16 | 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. |
Invitae | RCV001079456 | SCV000286423 | benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000241675 | SCV000317426 | benign | Cardiovascular phenotype | 2020-05-29 | criteria provided, single submitter | clinical testing | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance |
Eurofins Ntd Llc |
RCV000040989 | SCV000337108 | likely benign | not specified | 2016-08-02 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000082477 | SCV000493399 | benign | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | TTN: BS1, BS2 |
Athena Diagnostics Inc | RCV000082477 | SCV000844611 | benign | not provided | 2018-03-28 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000986935 | SCV001136094 | benign | Dilated cardiomyopathy 1G | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001128833 | SCV001288326 | benign | Tibial muscular dystrophy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV000986935 | SCV001295625 | benign | Dilated cardiomyopathy 1G | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001135821 | SCV001295626 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001135822 | SCV001295627 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001135823 | SCV001295628 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV001171215 | SCV001333917 | benign | Cardiomyopathy | 2017-11-28 | criteria provided, single submitter | clinical testing | |
Genetics and Genomics Program, |
RCV001293191 | SCV001434189 | likely benign | Primary dilated cardiomyopathy | criteria provided, single submitter | research | ||
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040989 | SCV001623316 | benign | not specified | 2021-04-20 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.99872T>C (p.Met33291Thr) results in a non-conservative amino acid change located in the M-band region (cardiodb.org) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 249108 control chromosomes, predominantly at a frequency of 0.0088 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 22.5- fold the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.99872T>C has been reported in the literature in individuals affected with Dilated Cardiomyopathy (e.g. Taylor_2011). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 11 other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign/likely benign (n=9) and uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as benign. |
Laboratory of Diagnostic Genome Analysis, |
RCV000082477 | SCV001799789 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000040989 | SCV001917755 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000082477 | SCV001928171 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000082477 | SCV001975336 | likely benign | not provided | no assertion criteria provided | clinical testing |