ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7964C>A (p.Ala2655Asp)

dbSNP: rs193922671
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001180106 SCV001344965 uncertain significance Cardiomyopathy 2019-12-06 criteria provided, single submitter clinical testing This missense variant replaces alanine with aspartic acid at codon 2655 of the DSP protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. A functional study has shown that this variant causes a partial reduction in intermediate filament binding (PMID: 30354334), however, clinical relevance of this observation is not known. This variant has been identified in compound heterozygosity with a pathogenic c.6310delA variant in an individual affected with cardiomyopathy, extensive mucocutaneous blisters, epidermolytic palmoplantar keratoderma, nail dystrophy, enamel dysplasia, and sparse woolly hair (PMID: 19924139). The proband's heterozygous parents and two siblings carrying the c.6310delA variant showed no skin or cardiac symptoms. This variant has not been identified 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.

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