Total submissions: 6
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, |
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. |
Gene |
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, |
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, |
RCV000786302 | SCV000925067 | uncertain significance | not provided | 2016-05-16 | no assertion criteria provided | provider interpretation |