ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.5329C>T (p.Arg1777Trp) (rs770329105)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819794 SCV000960475 pathogenic not provided 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1777 of the USH2A protein (p.Arg1777Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs770329105, ExAC 0.006%). This variant has been observed in several individuals with Usher syndrome or isolated retinitis pigmentosa (PMID: 21593743, 26969326, 22135276, 26629787). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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