Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156678 | SCV000206399 | likely benign | not specified | 2014-07-24 | criteria provided, single submitter | clinical testing | Arg778Gln in exon 10 of DFNB31: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, bushbaby, guinea pig, chinchilla, and brush-tailed rat have a glutamine (Gl n) at this position despite high nearby amino acid conservation. In addition, co mputational prediction tools do not suggest a high likelihood of impact to the p rotein. |
Invitae | RCV001326126 | SCV001517140 | uncertain significance | not provided | 2022-04-17 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs727505188, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 778 of the WHRN protein (p.Arg778Gln). ClinVar contains an entry for this variant (Variation ID: 179878). 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. This variant has not been reported in the literature in individuals affected with WHRN-related conditions. |