ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6778A>G (p.Ile2260Val)

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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 RCV002857084 SCV003222022 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2022-03-23 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. This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2260 of the DSP protein (p.Ile2260Val).
Ambry Genetics RCV003274053 SCV004007804 uncertain significance Cardiovascular phenotype 2023-04-06 criteria provided, single submitter clinical testing The p.I2260V variant (also known as c.6778A>G), located in coding exon 24 of the DSP gene, results from an A to G substitution at nucleotide position 6778. The isoleucine at codon 2260 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV004808375 SCV005429022 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-08-13 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 2260 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 not been identified 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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