ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1996G>C (p.Asp666His)

gnomAD frequency: 0.00001  dbSNP: rs771623047
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001179573 SCV001344265 uncertain significance Cardiomyopathy 2023-11-27 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with histidine at codon 666 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 not been reported in individuals affected with DSG2-related disorders in the literature. This variant has been identified in 2/249248 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.
Invitae RCV001875943 SCV002211020 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-03-07 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 920691). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs771623047, gnomAD 0.02%). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 666 of the DSG2 protein (p.Asp666His).

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