ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1768T>G (p.Cys590Gly)

dbSNP: rs1060503089
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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 RCV000458679 SCV000551829 uncertain significance Retinoblastoma 2022-11-22 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 not expected to disrupt RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 410944). 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 cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 590 of the RB1 protein (p.Cys590Gly).
Ambry Genetics RCV002402289 SCV002710644 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-05 criteria provided, single submitter clinical testing The p.C590G variant (also known as c.1768T>G), located in coding exon 18 of the RB1 gene, results from a T to G substitution at nucleotide position 1768. The cysteine at codon 590 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV000458679 SCV004825507 uncertain significance Retinoblastoma 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces cysteine with glycine at codon 590 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 RCV004568063 SCV005054154 uncertain significance Malignant tumor of urinary bladder 2023-12-05 criteria provided, single submitter clinical testing

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