ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4387G>A (p.Val1463Ile)

gnomAD frequency: 0.00003  dbSNP: rs948230523
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691670 SCV000819458 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2025-01-13 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001183077 SCV001348732 uncertain significance Cardiomyopathy 2023-08-10 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 1463 of the DSP 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 been reported in one individual affected with hypertrophic cardiomyopathy (PMID: 25351510). This variant has been identified in 8/282500 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 RCV002332430 SCV002632520 uncertain significance Cardiovascular phenotype 2020-06-24 criteria provided, single submitter clinical testing The p.V1463I variant (also known as c.4387G>A), located in coding exon 23 of the DSP gene, results from a G to A substitution at nucleotide position 4387. The valine at codon 1463 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301). This amino acid position is poorly 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.

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