Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001763634 | SCV002000988 | uncertain significance | not provided | 2020-04-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| Labcorp Genetics |
RCV003772024 | SCV004604466 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 557 of the DSP protein (p.Ile557Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1312628). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| All of Us Research Program, |
RCV004808115 | SCV005428835 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-06-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004995997 | SCV005575860 | uncertain significance | Cardiovascular phenotype | 2024-11-19 | criteria provided, single submitter | clinical testing | The p.I557T variant (also known as c.1670T>C), located in coding exon 13 of the DSP gene, results from a T to C substitution at nucleotide position 1670. The isoleucine at codon 557 is replaced by threonine, an amino acid with similar properties. This variant was reported in an individual in a peripartum cardiomyopathy cohort, but clinical details were limited (Goli R et al. Circulation, 2021 May;143:1852-1862). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |