ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1406C>A (p.Ser469Tyr)

dbSNP: rs1243796201
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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 RCV001345146 SCV001539248 uncertain significance Retinoblastoma 2022-03-07 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: 1041346). 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 serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 469 of the RB1 protein (p.Ser469Tyr).
Ambry Genetics RCV002395757 SCV002697797 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-21 criteria provided, single submitter clinical testing The p.S469Y variant (also known as c.1406C>A), located in coding exon 15 of the RB1 gene, results from a C to A substitution at nucleotide position 1406. The serine at codon 469 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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