ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1173C>A (p.Ser391Arg)

dbSNP: rs763242004
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000595774 SCV000704872 uncertain significance not provided 2017-01-13 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001181084 SCV001346160 uncertain significance Cardiomyopathy 2023-06-01 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 391 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 been reported in an individual affected with left ventricular non-compaction (PMID: 30471092). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001343860 SCV001537878 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-07-07 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 391 of the DSG2 protein (p.Ser391Arg). 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: 499401). 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).
Ambry Genetics RCV002331015 SCV002627616 uncertain significance Cardiovascular phenotype 2022-10-24 criteria provided, single submitter clinical testing The p.S391R variant (also known as c.1173C>A), located in coding exon 9 of the DSG2 gene, results from a C to A substitution at nucleotide position 1173. The serine at codon 391 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in a left ventricular non-compaction (LVNC) cohort; however, clinical details were limited (Richard P et al. Clin Genet, 2019 03;95:356-367). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004002460 SCV004819515 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 391 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 been reported in an individual affected with left ventricular non-compaction (PMID: 30471092). 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.

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