ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1429C>A (p.Pro477Thr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002392001 SCV002698699 uncertain significance Cardiovascular phenotype 2022-09-05 criteria provided, single submitter clinical testing The p.P477T variant (also known as c.1429C>A), located in coding exon 11 of the DSG2 gene, results from a C to A substitution at nucleotide position 1429. The proline at codon 477 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003103689 SCV003334033 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-10-23 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 477 of the DSG2 protein (p.Pro477Thr). 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. 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).

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