ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.692A>G (p.Tyr231Cys)

gnomAD frequency: 0.00001  dbSNP: rs770210088
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000423839 SCV000526983 uncertain significance not provided 2024-05-06 criteria provided, single submitter clinical testing Reported in cis with DSP p.(E323Q) in an individual with myocarditis and an individual with probable ARVC in the published literature (PMID: 33460606; 34552074); Observed with DSP p.(E323Q) in multiple individuals, suggesting these variants may be present in cis (on the same allele); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34352074, 33460606)
Labcorp Genetics (formerly Invitae), Labcorp RCV000526876 SCV000641339 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 RCV000771993 SCV000904948 uncertain significance Cardiomyopathy 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 231 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with myocarditis and arrhythmogenic right ventricular cardiomyopathy (PMID: 33460606). This variant has been identified in 3/282832 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.
AiLife Diagnostics, AiLife Diagnostics RCV000423839 SCV002501627 uncertain significance not provided 2021-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002374672 SCV002667478 uncertain significance Cardiovascular phenotype 2023-11-27 criteria provided, single submitter clinical testing The p.Y231C variant (also known as c.692A>G), located in coding exon 5 of the DSP gene, results from an A to G substitution at nucleotide position 692. The tyrosine at codon 231 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was reported to co-occur in cis with DSP p.E323Q in an individual with arrhythmogenic right ventricular cardiomyopathy (Scheel PJ et al. Am J Cardiol. 2021 Apr;145:128-134). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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