ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2332A>G (p.Thr778Ala)

gnomAD frequency: 0.00001  dbSNP: rs878853950
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000228067 SCV000284621 uncertain significance Retinoblastoma 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 778 of the RB1 protein (p.Thr778Ala). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 237669). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002444884 SCV002732968 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-24 criteria provided, single submitter clinical testing The p.T778A variant (also known as c.2332A>G), located in coding exon 23 of the RB1 gene, results from an A to G substitution at nucleotide position 2332. The threonine at codon 778 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.
Baylor Genetics RCV003463654 SCV004208529 uncertain significance Malignant tumor of urinary bladder 2023-07-20 criteria provided, single submitter clinical testing

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