ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.477T>A (p.Phe159Leu)

dbSNP: rs1952481513
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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 RCV001327710 SCV001518796 uncertain significance Retinoblastoma 2020-09-02 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 phenylalanine with leucine at codon 159 of the RB1 protein (p.Phe159Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine.
Ambry Genetics RCV002329296 SCV002634537 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-20 criteria provided, single submitter clinical testing The p.F159L variant (also known as c.477T>A), located in coding exon 4 of the RB1 gene, results from a T to A substitution at nucleotide position 477. The phenylalanine at codon 159 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly 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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