ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2518G>C (p.Gly840Arg)

dbSNP: rs374157786
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038781 SCV001202274 uncertain significance Retinoblastoma 2023-01-16 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: 837445). 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 glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 840 of the RB1 protein (p.Gly840Arg).
Ambry Genetics RCV002427492 SCV002742007 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-17 criteria provided, single submitter clinical testing The p.G840R variant (also known as c.2518G>C), located in coding exon 24 of the RB1 gene, results from a G to C substitution at nucleotide position 2518. The glycine at codon 840 is replaced by arginine, an amino acid with 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.
All of Us Research Program, National Institutes of Health RCV001038781 SCV004838212 uncertain significance Retinoblastoma 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 840 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004768800 SCV005376343 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 33868464, 23516486)

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