Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000216384 | SCV000271168 | likely benign | not specified | 2016-01-07 | criteria provided, single submitter | clinical testing | p.Arg1438Lys is exon 20 of USH2A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, 4 mammals (white rhinoceros, star-nosed mole, tenrec, wallaby) have a Lys ine (Lys) at this position despite high nearby amino acid conservation. In addit ion, computational analyses do not suggest a high likelihood of impact to the pr otein. |
Invitae | RCV001368743 | SCV001565151 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1438 of the USH2A protein (p.Arg1438Lys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 228214). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine 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. |