ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1493A>G (p.Tyr498Cys)

dbSNP: rs1948523564
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001215038 SCV001386757 uncertain significance Retinoblastoma 2022-11-01 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 944607). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 498 of the RB1 protein (p.Tyr498Cys).
Ambry Genetics RCV003163649 SCV003871184 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-08 criteria provided, single submitter clinical testing The p.Y498C variant (also known as c.1493A>G), located in coding exon 16 of the RB1 gene, results from an A to G substitution at nucleotide position 1493. The tyrosine at codon 498 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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