Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000148472 | SCV000051376 | likely benign | Arrhythmogenic right ventricular cardiomyopathy | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000037262 | SCV000060919 | likely benign | not specified | 2015-04-03 | criteria provided, single submitter | clinical testing | p.Val392Ile in exon 9 of DSG2: This variant has been reported in many individual s with diverse presentations (ARVC, LQTS1, LDAC, DCM: Syrris 2007, Bhuiyan 2009, Bauce 2010, Klauke 2010, Quarta 2011, Cox 2011, Bauce 2011, Garcia-Parva 2011, LMM unpublished data). However, this variant has also been identified in 0.7% (1 11/16510) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org;dbSNP rs193922639). In addition, valine (Val) at position 392 is poorly conserved in evolution and the variant is present in two species (including 1 mammal), suggesting that a change to this position may be t olerated. In summary, this variant is likely benign but a modifying role cannot be excluded. |
CSER _CC_NCGL, |
RCV000148472 | SCV000190173 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2014-06-01 | criteria provided, single submitter | research | Low GERP score may suggest that this variant may belong in a lower pathogenicity class |
Gene |
RCV000472660 | SCV000233494 | benign | not provided | 2020-09-08 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 23812740, 26899768, 25637381, 23299917, 21636032, 24070718, 17105751, 20031616, 20129281, 20829228, 21606390, 21859740, 21606396, 21723241, 23071725, 23396983, 24436435, 24055113, 26138720, 26681313, 27153395, 25985138, 28255936, 29062102, 30885746) |
Labcorp Genetics |
RCV001081298 | SCV000561397 | benign | Arrhythmogenic right ventricular dysplasia 10 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000037262 | SCV000697880 | benign | not specified | 2019-08-26 | criteria provided, single submitter | clinical testing | Variant summary: DSG2 c.1174G>A (p.Val392Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0022 in 249420 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 200 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSG2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. Though c.1174G>A has been reported in the literature in individuals affected with ARVC/D, LQTS and DCM, including families showing incomplete co-segregation with disease, in addition, multiple co-occurrences with other pathogenic variants have been noted (PKP2 c.148_151delACAG (p.Thr50fsX61), Bauce_2010, Rigato_2013; PKP2 c.235C>T (p.Arg79X), Cox _2011), providing supporting evidence for a benign role. Publication also reported experimental evidence evaluating an impact on protein function, and demonstrated no damaging effect of this variant (Gaertner_2012, Dieding_2017). Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as Benign (2x), Likely benign (3x) or VUS (1x). Based on the evidence outlined above, the variant was classified as benign. |
Ambry Genetics | RCV000619528 | SCV000734934 | likely benign | Cardiovascular phenotype | 2018-06-08 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
CHEO Genetics Diagnostic Laboratory, |
RCV000029667 | SCV000901998 | benign | Cardiomyopathy | 2018-07-25 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000029667 | SCV000902997 | benign | Cardiomyopathy | 2018-06-11 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000472660 | SCV001135117 | benign | not provided | 2023-08-22 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256759 | SCV001433191 | benign | Arrhythmogenic right ventricular dysplasia 1 | 2019-07-25 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000472660 | SCV001474568 | likely benign | not provided | 2023-06-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000472660 | SCV004140913 | likely benign | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | DSG2: BP4, BS2 |
All of Us Research Program, |
RCV000148472 | SCV005428698 | benign | Arrhythmogenic right ventricular cardiomyopathy | 2024-09-24 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV000472660 | SCV001739689 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000037262 | SCV001924013 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000037262 | SCV001929572 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000037262 | SCV001959098 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000472660 | SCV001965704 | likely benign | not provided | no assertion criteria provided | clinical testing |