ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1732A>C (p.Lys578Gln)

gnomAD frequency: 0.00002  dbSNP: rs761478865
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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 RCV001924802 SCV002155633 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-02-03 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 578 of the DSP protein (p.Lys578Gln). 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1384315). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is present in population databases (rs761478865, gnomAD 0.002%).
Ambry Genetics RCV002406993 SCV002715694 uncertain significance Cardiovascular phenotype 2018-11-09 criteria provided, single submitter clinical testing The p.K578Q variant (also known as c.1732A>C), located in coding exon 14 of the DSP gene, results from an A to C substitution at nucleotide position 1732. The lysine at codon 578 is replaced by glutamine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, glutamine is the reference amino acid in other 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.
All of Us Research Program, National Institutes of Health RCV004010762 SCV004832967 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-04-10 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamine at codon 578 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 not been reported in individuals affected with DSP-related disorders in the literature. This variant has been identified in 2/282714 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.

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