ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13430A>G (p.Tyr4477Cys)

gnomAD frequency: 0.00001  dbSNP: rs921800139
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Total submissions: 4
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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 RCV000826080 SCV000967575 uncertain significance not specified 2019-02-26 criteria provided, single submitter clinical testing The p.Tyr4477Cys variant in USH2A has not been previously reported in individuals with hearing loss or Usher syndrome but has been identified in 0.006% (1/16230) African chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3.
Blueprint Genetics RCV001075631 SCV001241258 uncertain significance Retinal dystrophy 2019-02-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001361727 SCV001557714 pathogenic not provided 2023-10-09 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 4477 of the USH2A protein (p.Tyr4477Cys). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of Usher syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 667358). 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. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001830848 SCV002088262 uncertain significance Usher syndrome type 2A 2021-07-27 no assertion criteria provided clinical testing

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