ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5291T>C (p.Leu1764Pro)

dbSNP: rs767885673
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory - Cardiogenetics, CHU de Nantes RCV002260450 SCV002540070 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2022-06-01 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV004005569 SCV004833327 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-07-10 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 1764 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 an individual affected with long QT syndrome, who also carried a pathogenic variant in the KCNQ1 gene that could explain the observed phenotype (PMID: 29511324). This variant has been identified in 2/250562 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005213635 SCV005861268 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-08-12 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1764 of the DSP protein (p.Leu1764Pro). This variant is present in population databases (rs767885673, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1693190). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

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