Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001182549 | SCV001348022 | uncertain significance | Cardiomyopathy | 2023-05-10 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with serine at codon 2593 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 been reported in an individual affected with sudden explained death (PMID: 29247119). This variant has been identified in 1/251476 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. |
Invitae | RCV001876062 | SCV002227639 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2021-06-17 | 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with sudden unexplained death (PMID: 29247119). ClinVar contains an entry for this variant (Variation ID: 922453). This variant is present in population databases (rs563272509, ExAC 0.001%). This sequence change replaces isoleucine with serine at codon 2593 of the DSP protein (p.Ile2593Ser). The isoleucine residue is moderately conserved and there is a large physicochemical difference between isoleucine and serine. |
Ambry Genetics | RCV002411689 | SCV002674687 | uncertain significance | Cardiovascular phenotype | 2022-03-25 | criteria provided, single submitter | clinical testing | The p.I2593S variant (also known as c.7778T>G), located in coding exon 24 of the DSP gene, results from a T to G substitution at nucleotide position 7778. The isoleucine at codon 2593 is replaced by serine, an amino acid with dissimilar properties. This alteration has been reported in a sudden unexplained death cohort; however, clinical details were limited (Lin Y et al. Circ Cardiovasc Genet, 2017 Dec;10:[ePub ahead of print]). This amino acid position is not well 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, |
RCV002505774 | SCV002814601 | 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 | 2021-08-27 | criteria provided, single submitter | clinical testing |