ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1465T>G (p.Cys489Gly)

dbSNP: rs1948523129
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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 RCV001312801 SCV001503272 uncertain significance Retinoblastoma 2020-05-30 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, but 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 cysteine with glycine at codon 489 of the RB1 protein (p.Cys489Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine.
Ambry Genetics RCV003294256 SCV004001590 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter clinical testing The p.C489G variant (also known as c.1465T>G), located in coding exon 16 of the RB1 gene, results from a T to G substitution at nucleotide position 1465. The cysteine at codon 489 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004590317 SCV005081339 uncertain significance not provided 2023-08-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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