ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.12268C>A (p.Pro4090Thr) (rs780893919)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665136 SCV000789202 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-01-20 criteria provided, single submitter clinical testing
Invitae RCV001245259 SCV001418534 uncertain significance not provided 2019-09-06 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 4090 of the USH2A protein (p.Pro4090Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs780893919, ExAC 0.003%). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 23591405). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 550401). 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. This variant disrupts the p.Pro4090 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 28559085), which suggests that this may be a clinically significant amino acid residue. 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.
Sharon lab,Hadassah-Hebrew University Medical Center RCV001003257 SCV001161339 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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