Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150563 | SCV000197813 | uncertain significance | not specified | 2013-09-18 | criteria provided, single submitter | clinical testing | Ile950Met variant in DSP has not been previously reported in individuals with ca rdiomyopathy or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest th at the Ile950Met variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Additional information is neede d to fully assess the clinical significance of the Ile950Met variant. |
Invitae | RCV001850046 | SCV002219706 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002433647 | SCV002749872 | uncertain significance | Cardiovascular phenotype | 2020-02-05 | criteria provided, single submitter | clinical testing | The p.I950M variant (also known as c.2850T>G), located in coding exon 20 of the DSP gene, results from a T to G substitution at nucleotide position 2850. The isoleucine at codon 950 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is poorly 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. |
Fulgent Genetics, |
RCV002483305 | SCV002777392 | 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 | 2021-09-14 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV003531970 | SCV004363345 | uncertain significance | Cardiomyopathy | 2023-11-08 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 950 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 1/250032 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. |