Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001576476 | SCV001803677 | likely benign | not provided | 2020-12-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001576476 | SCV002282492 | uncertain significance | not provided | 2022-04-29 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs76626460, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1208227). This variant has not been reported in the literature in individuals affected with DIAPH3-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1118 of the DIAPH3 protein (p.Arg1118Cys). |