ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1627G>A (p.Gly543Ser)

gnomAD frequency: 0.00001  dbSNP: rs1418248949
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000792534 SCV000931837 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 543 of the DSC2 protein (p.Gly543Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 639675). 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. 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.
Color Diagnostics, LLC DBA Color Health RCV001184155 SCV001350072 uncertain significance Cardiomyopathy 2021-01-27 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 543 of the DSC2 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 been identified in 1/251180 chromosomes 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.
Ambry Genetics RCV002536943 SCV003535481 uncertain significance Inborn genetic diseases 2022-02-11 criteria provided, single submitter clinical testing The c.1627G>A (p.G543S) alteration is located in exon 11 (coding exon 11) of the DSC2 gene. This alteration results from a G to A substitution at nucleotide position 1627, causing the glycine (G) at amino acid position 543 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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