ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1573G>A (p.Ala525Thr) (rs587778640)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701091 SCV000829874 uncertain significance Retinoblastoma 2018-06-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 525 of the RB1 protein (p.Ala525Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs587778640, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with RB1-related disease. ClinVar contains an entry for this variant (Variation ID: 135119). 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.
ITMI RCV000121919 SCV000086124 not provided not specified 2013-09-19 no assertion provided reference population

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