ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.10421A>G (p.Tyr3474Cys) (rs749121941)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669541 SCV000794302 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-10-05 criteria provided, single submitter clinical testing
Invitae RCV001242045 SCV001415107 uncertain significance not provided 2019-10-22 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 3474 of the USH2A protein (p.Tyr3474Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs749121941, ExAC 0.002%). This variant has been observed in individuals affected with autosomal recessive retinitis pigmentosa or Usher syndrome (PMID: 27318125, 24265693, Invitae). ClinVar contains an entry for this variant (Variation ID: 553994). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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