Submissions for variant NM_001943.5(DSG2):c.296T>A (p.Phe99Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1275376903

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770544	SCV000901991	uncertain significance	Cardiomyopathy	2016-12-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000770544	SCV001344011	uncertain significance	Cardiomyopathy	2022-12-27	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with tyrosine at codon 99 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae	RCV001855728	SCV002215424	uncertain significance	Arrhythmogenic right ventricular dysplasia 10	2022-12-16	criteria provided, single submitter	clinical testing	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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 626838). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 99 of the DSG2 protein (p.Phe99Tyr).
Fulgent Genetics, Fulgent Genetics	RCV002487573	SCV002787769	uncertain significance	Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB	2021-11-22	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003999949	SCV004819431	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2023-12-07	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with tyrosine at codon 99 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.