ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3118G>A (p.Val1040Ile)

gnomAD frequency: 0.00004  dbSNP: rs201966605
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001704861 SCV000233472 likely benign not provided 2020-02-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000642312 SCV000763981 likely benign Arrhythmogenic right ventricular dysplasia 10 2023-10-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001183736 SCV001349550 likely benign Cardiomyopathy 2019-11-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV003298229 SCV003996709 likely benign Cardiovascular phenotype 2023-06-14 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004700546 SCV005202223 likely benign not specified 2024-07-30 criteria provided, single submitter clinical testing Variant summary: DSG2 c.3118G>A (p.Val1040Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-05 in 249444 control chromosomes, predominantly at a frequency of 0.001 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSG2 causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.00025). c.3118G>A has been reported in the literature in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy or sudden unexplained death (Wada_2017, Hata_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: 27135274, 29178656). ClinVar contains an entry for this variant (Variation ID: 199794). Based on the evidence outlined above, the variant was classified as likely benign.

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