ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.818C>T (p.Pro273Leu)

gnomAD frequency: 0.00003  dbSNP: rs864622708
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204467 SCV000261982 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2023-11-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 273 of the DSC2 protein (p.Pro273Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 220972). 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 expected to disrupt DSC2 protein function with a positive predictive value of 80%. 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.
Ambry Genetics RCV002426970 SCV002681186 uncertain significance Cardiovascular phenotype 2020-03-31 criteria provided, single submitter clinical testing The p.P273L variant (also known as c.818C>T), located in coding exon 7 of the DSC2 gene, results from a C to T substitution at nucleotide position 818. The proline at codon 273 is replaced by leucine, an amino acid with similar properties. This amino acid position is well 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.
PreventionGenetics, part of Exact Sciences RCV003977573 SCV004791364 uncertain significance DSC2-related condition 2023-12-13 criteria provided, single submitter clinical testing The DSC2 c.818C>T variant is predicted to result in the amino acid substitution p.Pro273Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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