ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.679A>G (p.Ile227Val)

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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 RCV003099072 SCV003480729 uncertain significance Retinoblastoma 2022-04-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 227 of the RB1 protein (p.Ile227Val). 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. 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).
Ambry Genetics RCV003294500 SCV004002015 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-03 criteria provided, single submitter clinical testing The p.I227V variant (also known as c.679A>G), located in coding exon 7 of the RB1 gene, results from an A to G substitution at nucleotide position 679. The isoleucine at codon 227 is replaced by valine, an amino acid with highly similar 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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