ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3877A>G (p.Ile1293Val)

gnomAD frequency: 0.00002  dbSNP: rs376555665
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000254437 SCV000318768 uncertain significance Cardiovascular phenotype 2013-09-03 criteria provided, single submitter clinical testing The p.I1293V variant (also known as c.3877A>G) is located in coding exon 23 of the DSPgene. This alteration results from a A to G substitution at nucleotide position 3877. The isoleucine at codon 1293 is replaced by valine, an amino acid with highly similar properties. Based on data from the NHLBI Exome Sequencing Project (ESP), the G-allele has an overall frequency of approximately0.01% (1/13006), having been observed in0.01% (1/8600)of European American alleles, and not observed in 4406 African American alleles studied.This variant was not reported in population-based cohorts in the Database of Single Nucleotide Polymorphisms (dbSNP) or the 1000 Genomes Project.Based on protein sequence alignment, thisamino acid position is not well conserved in available vertebrate species, with valine as the reference amino acid in four species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively.Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV000473064 SCV000543263 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-12-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001183997 SCV001349865 uncertain significance Cardiomyopathy 2022-12-02 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1293 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 cardiovascular 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.
GeneDx RCV000786302 SCV002102683 uncertain significance not provided 2022-02-21 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Fulgent Genetics, Fulgent Genetics RCV002479978 SCV002776000 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis 2021-11-11 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786302 SCV000925067 uncertain significance not provided 2016-05-16 no assertion criteria provided provider interpretation

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