ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1741G>A (p.Gly581Arg)

gnomAD frequency: 0.00001  dbSNP: rs375645171
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001012919 SCV001173439 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-17 criteria provided, single submitter clinical testing The p.G581R variant (also known as c.1741G>A), located in coding exon 18 of the RB1 gene, results from a G to A substitution at nucleotide position 1741. The glycine at codon 581 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001054750 SCV001219100 uncertain significance Retinoblastoma 2023-08-07 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 819952). 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 581 of the RB1 protein (p.Gly581Arg).
All of Us Research Program, National Institutes of Health RCV001054750 SCV004832575 uncertain significance Retinoblastoma 2023-07-22 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 581 of the RB1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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.
Baylor Genetics RCV004569911 SCV005054123 uncertain significance Malignant tumor of urinary bladder 2024-02-29 criteria provided, single submitter clinical testing

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