Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001195477 | SCV001365854 | likely benign | not specified | 2020-01-15 | criteria provided, single submitter | clinical testing | The p.Tyr1376His variant in USH2A is classified as likely benign due to a lack of conservation across species. Over 10 mammals harbor a histidine (His) at this position despite high nearby amino acid conservation. ACMG/AMP Criteria applied: BP4_Strong. |
Invitae | RCV002559239 | SCV003296532 | uncertain significance | not provided | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with histidine at codon 1376 of the USH2A protein (p.Tyr1376His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs374449657, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. 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 histidine 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. |