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

gnomAD frequency: 0.00008  dbSNP: rs767979763

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705065	SCV000834045	uncertain significance	Arrhythmogenic right ventricular dysplasia 10	2024-08-20	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). Invitae Evidence 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 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: 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.
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
Color Diagnostics, LLC DBA Color Health	RCV005401584	SCV006061379	likely benign	Cardiomyopathy	2024-05-23	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV002424708	SCV006067565	uncertain significance	Cardiovascular phenotype	2025-04-09	criteria provided, single submitter	clinical testing