ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1961T>C (p.Val654Ala)

dbSNP: rs769113950
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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 RCV000703311 SCV000832207 uncertain significance Retinoblastoma 2022-07-19 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 579914). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (rs769113950, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 654 of the RB1 protein (p.Val654Ala).
Ambry Genetics RCV002422584 SCV002721447 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-06 criteria provided, single submitter clinical testing The p.V654A variant (also known as c.1961T>C) is located in coding exon 20 of the RB1 gene. The valine at codon 654 is replaced by alanine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 20. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.

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