ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1751G>T (p.Cys584Phe)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001216713 SCV001388523 pathogenic not provided 2019-06-06 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 584 of the USH2A protein (p.Cys584Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Usher syndrome type II in a family and has been reported in combination with another USH2A variant in an unrelated individual affected with this disease (PMID: 24516651, 26075083). 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 (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. For these reasons, this variant has been classified as Pathogenic.

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