ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.1724G>A (p.Cys575Tyr) (rs483353054)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667787 SCV000792291 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-06-14 criteria provided, single submitter clinical testing
Invitae RCV001067227 SCV001232274 pathogenic not provided 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 575 of the USH2A protein (p.Cys575Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs483353054, ExAC 0.001%). This variant has been observed in several individuals affected with Usher syndrome (PMID: 21569298, 25425308, 28894305, 24944099). ClinVar contains an entry for this variant (Variation ID: 552511). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys575 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 15325563), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073924 SCV001239489 pathogenic Retinal dystrophy 2018-06-26 criteria provided, single submitter clinical testing

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