Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000490099 | SCV000577006 | uncertain significance | not provided | 2017-04-13 | criteria provided, single submitter | clinical testing | The E2629K variant of uncertain significance in the DSP gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E2629K variant was is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E2629K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity. |
| Invitae | RCV000814164 | SCV000954565 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-02-04 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 426538). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is present in population databases (rs756976948, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2629 of the DSP protein (p.Glu2629Lys). |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000490099 | SCV000925066 | uncertain significance | not provided | 2017-08-16 | no assertion criteria provided | provider interpretation |