Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001935171 | SCV002170893 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2021-04-29 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DSP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 2416 of the DSP protein (p.Phe2416Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. |
| All of Us Research Program, |
RCV004010838 | SCV004839287 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2023-10-06 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with leucine at codon 2416 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 DSP-related 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 |
RCV004820217 | SCV005441430 | uncertain significance | not provided | 2024-06-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |