ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.154A>G (p.Thr52Ala)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003176985 SCV003854385 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-16 criteria provided, single submitter clinical testing The p.T52A variant (also known as c.154A>G), located in coding exon 2 of the RB1 gene, results from an A to G substitution at nucleotide position 154. The threonine at codon 52 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003514613 SCV004319310 uncertain significance Retinoblastoma 2023-01-20 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 alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 52 of the RB1 protein (p.Thr52Ala).

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