ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1789C>A (p.Gln597Lys)

dbSNP: rs1566233076
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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 RCV001954492 SCV002195023 uncertain significance Retinoblastoma 2022-10-27 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 597 of the RB1 protein (p.Gln597Lys). 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: 1418955). 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).
All of Us Research Program, National Institutes of Health RCV001954492 SCV004824928 uncertain significance Retinoblastoma 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 597 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.
Ambry Genetics RCV004043996 SCV005034551 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-02 criteria provided, single submitter clinical testing The p.Q597K variant (also known as c.1789C>A), located in coding exon 18 of the RB1 gene, results from a C to A substitution at nucleotide position 1789. The glutamine at codon 597 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.

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