ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1548C>G (p.Asn516Lys)

dbSNP: rs1407207091
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001182859 SCV001348455 uncertain significance Cardiomyopathy 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces asparagine with lysine at codon 516 of the DSP protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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.
Invitae RCV001876076 SCV002191886 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-02-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 516 of the DSP protein (p.Asn516Lys). This variant is not present in population databases (gnomAD no frequency). 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: 922672). 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. 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.
Ambry Genetics RCV002402541 SCV002710118 uncertain significance Cardiovascular phenotype 2020-12-24 criteria provided, single submitter clinical testing The p.N516K variant (also known as c.1548C>G), located in coding exon 12 of the DSP gene, results from a C to G substitution at nucleotide position 1548. The asparagine at codon 516 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly 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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