Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522123 | SCV000619641 | uncertain significance | not provided | 2017-08-03 | criteria provided, single submitter | clinical testing | The I246V variant in the USH2A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I246V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I246V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret I246V as a variant of uncertain significance. |
Blueprint Genetics | RCV001073710 | SCV001239269 | uncertain significance | Retinal dystrophy | 2017-07-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000522123 | SCV003468336 | uncertain significance | not provided | 2022-05-03 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 246 of the USH2A protein (p.Ile246Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 451003). 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 valine 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. |
Genome- |
RCV003449492 | SCV004182952 | uncertain significance | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001829504 | SCV004182953 | uncertain significance | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001829504 | SCV002094017 | uncertain significance | Usher syndrome type 2A | 2020-02-21 | no assertion criteria provided | clinical testing |