ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9842G>T (p.Cys3281Phe) (rs727504654)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155917 SCV000205628 uncertain significance not specified 2013-09-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Cys3281Phe variant in USH2A has been previously reported in an individual with clinical fea tures of Usher syndrome, but a second variant in the USH2A gene was not identifi ed (Le Quesne Stabej 2012). This variant was not observed in large population st udies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant c annot be determined with certainty; however, based upon its presence in an affec ted individual and its absence from the general population, we lean towards a mo re likely pathogenic role.
Counsyl RCV000666703 SCV000791045 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-04-24 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000666703 SCV000894748 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2018-10-31 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074861 SCV001240464 uncertain significance Retinal dystrophy 2019-07-31 criteria provided, single submitter clinical testing
Invitae RCV001227049 SCV001399385 uncertain significance not provided 2019-10-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 3281 of the USH2A protein (p.Cys3281Phe). 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 in an individual with clinical features of Usher syndrome (PMID: 27208204). ClinVar contains an entry for this variant (Variation ID: 179132). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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