ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.959G>T (p.Arg320Leu)

dbSNP: rs760787104
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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 RCV000700340 SCV000829092 uncertain significance Retinoblastoma 2022-05-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 320 of the RB1 protein (p.Arg320Leu). This variant is not present in population databases (gnomAD no frequency). 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: 577551). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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 RCV002369921 SCV002690619 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-23 criteria provided, single submitter clinical testing The p.R320L variant (also known as c.959G>T), located in coding exon 10 of the RB1 gene, results from a G to T substitution at nucleotide position 959. The arginine at codon 320 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. 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.
All of Us Research Program, National Institutes of Health RCV000700340 SCV004844640 uncertain significance Retinoblastoma 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 320 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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.
Baylor Genetics RCV004569361 SCV005054141 uncertain significance Malignant tumor of urinary bladder 2024-01-20 criteria provided, single submitter clinical testing

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