ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8216C>T (p.Pro2739Leu)

gnomAD frequency: 0.00001  dbSNP: rs761527198
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001180460 SCV001345393 uncertain significance Cardiomyopathy 2023-02-21 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 2739 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 not been reported in individuals affected with DSP-related disorders in the literature. This variant has been identified in 1/251418 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 RCV002429808 SCV002681248 uncertain significance Cardiovascular phenotype 2022-09-05 criteria provided, single submitter clinical testing The p.P2739L variant (also known as c.8216C>T), located in coding exon 24 of the DSP gene, results from a C to T substitution at nucleotide position 8216. The proline at codon 2739 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002560803 SCV003271858 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2022-11-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 921195). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is present in population databases (rs761527198, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2739 of the DSP protein (p.Pro2739Leu).
All of Us Research Program, National Institutes of Health RCV004803468 SCV005424622 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-09-23 criteria provided, single submitter clinical testing

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