ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2506C>G (p.Leu836Val)

gnomAD frequency: 0.00011  dbSNP: rs767979763
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705065 SCV000834045 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 836 of the DSG2 protein (p.Leu836Val). This variant is present in population databases (rs767979763, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 581285). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSG2 protein function. 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223925 SCV002501917 uncertain significance not provided 2021-08-20 criteria provided, single submitter clinical testing
GeneDx RCV002223925 SCV002568704 uncertain significance not provided 2022-08-09 criteria provided, single submitter clinical testing Reported in one adult patient with non-specific cardiomyopathy and ventricular tachycardia (Seidelmann et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28087566)
Ambry Genetics RCV002424708 SCV002742363 likely benign Cardiovascular phenotype 2022-12-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Fulgent Genetics, Fulgent Genetics RCV002485760 SCV002790505 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-09-24 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV002223925 SCV004224475 uncertain significance not provided 2023-02-24 criteria provided, single submitter clinical testing

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