ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.1550G>C (p.Arg517Thr) (rs1393503590)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668092 SCV000792640 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-07-05 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075316 SCV001240934 uncertain significance Retinal dystrophy 2018-01-04 criteria provided, single submitter clinical testing
Invitae RCV001230842 SCV001403340 uncertain significance not provided 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 517 of the USH2A protein (p.Arg517Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant also falls at the last nucleotide of exon 8 of the USH2A coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with either Usher syndrome or non-syndromic retinitis pigmentosa, and to segregate with Usher syndrome in a family (PMID: 15325563, 20507924, 15671307). ClinVar contains an entry for this variant (Variation ID: 552769). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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