ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.142C>T (p.Leu48Phe)

dbSNP: rs769776739
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476734 SCV000551485 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2022-10-07 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 DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 410649). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs769776739, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 48 of the DSC2 protein (p.Leu48Phe).
Color Diagnostics, LLC DBA Color Health RCV001181378 SCV001346512 likely benign Cardiomyopathy 2019-11-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002393146 SCV002698488 uncertain significance Cardiovascular phenotype 2020-06-15 criteria provided, single submitter clinical testing The p.L48F variant (also known as c.142C>T), located in coding exon 2 of the DSC2 gene, results from a C to T substitution at nucleotide position 142. The leucine at codon 48 is replaced by phenylalanine, an amino acid with highly similar properties. 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.

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