ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9885T>G (p.Cys3295Trp)

dbSNP: rs780036975
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001067445 SCV001232510 pathogenic not provided 2024-12-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 3295 of the USH2A protein (p.Cys3295Trp). This variant is present in population databases (rs780036975, gnomAD 0.007%). This missense change has been observed in individual(s) with retinitis pigmentosa and/or USH2A-related conditions (internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 861026). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. This variant disrupts the p.Cys3295 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 30902645; internal data), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001067445 SCV001820598 likely pathogenic not provided 2020-05-08 criteria provided, single submitter clinical testing Reported in association with late-onset Usher syndrome (Vezinaw et al., 2019); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30796641)
Genome-Nilou Lab RCV003455293 SCV004182637 likely pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing

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