Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172530 | SCV000050911 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000037272 | SCV000060929 | uncertain significance | not specified | 2014-08-27 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Leu594Pro varia nt in DSG2 has been identified in 4/8470 European American chromosomes by the NH LBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs19968190 1). Our laboratory has previously detected this variant in 3 individuals (1 Asia n child with HCM and WPW, 1 Ashkenazi Jewish adult with possible DCM/ARVC, and 1 Ashkenazi Jewish adult with HCM). Leucine (Leu) at position 594 is not conserve d in mammals or evolutionarily distant species, raising the possibility that a c hange at this position may be tolerated. Additional computational prediction too ls suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clini cal significance of the Leu594Pro variant is uncertain, these data suggest that it is more likely to be benign. |
Labcorp Genetics |
RCV001085411 | SCV000561400 | likely benign | Arrhythmogenic right ventricular dysplasia 10 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000037272 | SCV000714372 | likely benign | not specified | 2018-01-22 | 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. |
Ambry Genetics | RCV000618191 | SCV000735732 | likely benign | Cardiovascular phenotype | 2018-03-07 | 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. |
Color Diagnostics, |
RCV000776195 | SCV000911324 | benign | Cardiomyopathy | 2018-08-14 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852742 | SCV000995459 | likely benign | Primary dilated cardiomyopathy | 2018-04-06 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001085411 | SCV001286958 | benign | Arrhythmogenic right ventricular dysplasia 10 | 2018-05-11 | 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. |
Ce |
RCV000172530 | SCV002822452 | likely benign | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | DSG2: BP4 |
CHEO Genetics Diagnostic Laboratory, |
RCV000776195 | SCV003838788 | likely benign | Cardiomyopathy | 2021-08-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000037272 | SCV004241802 | likely benign | not specified | 2023-12-04 | criteria provided, single submitter | clinical testing | Variant summary: DSG2 c.1781T>C (p.Leu594Pro) results in a non-conservative amino acid change in 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 0.00063 in 249162 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 2.52 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSG2 causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.00025), suggesting that the variant is benign. c.1781T>C has been reported in the literature in a heterozygous individual affected with Brugada syndrome (e.g. DiResta_2015) and in a case of sudden infant death syndrome reported as a VUS (e.g. Neubauer_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26220970, 21636032, 28074886). Twelve submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, classifying the variant as benign (n=3), likely benign (n=8), or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
Clinical Genetics, |
RCV000037272 | SCV001924538 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000172530 | SCV001975715 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
RCV003952429 | SCV004768410 | likely benign | DSG2-related disorder | 2024-02-13 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |