ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1139A>G (p.Tyr380Cys)

gnomAD frequency: 0.00001  dbSNP: rs111033395
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041694 SCV000065390 uncertain significance not specified 2008-06-11 criteria provided, single submitter clinical testing
Invitae RCV001852855 SCV002257447 pathogenic not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 380 of the USH2A protein (p.Tyr380Cys). This variant is present in population databases (rs111033395, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of USH2A-related conditions (PMID: 35266249, 37287646; Invitae). 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: 48373). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana RCV002307376 SCV002600269 pathogenic Usher syndrome type 2 2022-11-14 no assertion criteria provided clinical testing Novel pathogenic variant. PP4 (manual), PM3 (manual), PM2 , PP3, PP5. https://franklin.genoox.com/clinical-db/variant/snp/chr1-216498651-T-C

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