ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.699G>A (p.Met233Ile)

dbSNP: rs1952626050
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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 RCV001347440 SCV001541700 uncertain significance Retinoblastoma 2022-06-23 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 233 of the RB1 protein (p.Met233Ile). This variant has not been reported in the literature in individuals affected with RB1-related conditions. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1043349).
Ambry Genetics RCV003169698 SCV003913087 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-23 criteria provided, single submitter clinical testing The p.M233I variant (also known as c.699G>A), located in coding exon 7 of the RB1 gene, results from a G to A substitution at nucleotide position 699. The methionine at codon 233 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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