Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000208142 | SCV000263883 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2015-12-03 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000220371 | SCV000271743 | uncertain significance | not specified | 2015-03-04 | criteria provided, single submitter | clinical testing | The p.Val2642Ile variant in DSP has not been previously identified in individual s with cardiomyopathy or in large population studies. Computational prediction t ools and conservation analysis does not provide strong evidence for or against a n impact the protein. In summary, the clinical significance of the p.Val2642Ile variant is uncertain. |
Labcorp Genetics |
RCV000469566 | SCV000543234 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-05-05 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001185751 | SCV001352026 | uncertain significance | Cardiomyopathy | 2023-03-09 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 2642 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 been identified in 4/250910 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. |
Gene |
RCV001762452 | SCV001990835 | uncertain significance | not provided | 2019-04-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID 222587; Landrum et al., 2016) |
Fulgent Genetics, |
RCV002485359 | SCV002786190 | 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 | 2021-10-11 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001185751 | SCV003837793 | uncertain significance | Cardiomyopathy | 2021-11-16 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000220371 | SCV003844632 | uncertain significance | not specified | 2023-02-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003298272 | SCV003996575 | uncertain significance | Cardiovascular phenotype | 2023-04-06 | criteria provided, single submitter | clinical testing | The p.V2642I variant (also known as c.7924G>A), located in coding exon 24 of the DSP gene, results from a G to A substitution at nucleotide position 7924. The valine at codon 2642 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). 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. |
All of Us Research Program, |
RCV003997683 | SCV004816637 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-08-06 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 2642 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 been identified in 4/250910 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. |