ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.734C>T (p.Pro245Leu)

dbSNP: rs2138112166
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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 RCV001977132 SCV002251826 uncertain significance Retinoblastoma 2021-01-26 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 245 of the RB1 protein (p.Pro245Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. 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, 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.
Ambry Genetics RCV004656797 SCV005160550 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-10 criteria provided, single submitter clinical testing The p.P245L variant (also known as c.734C>T), located in coding exon 8 of the RB1 gene, results from a C to T substitution at nucleotide position 734. The proline at codon 245 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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