ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2735A>G (p.Gln912Arg)

dbSNP: rs1949528429
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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 RCV001314437 SCV001504971 uncertain significance Retinoblastoma 2023-09-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 912 of the RB1 protein (p.Gln912Arg). 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: 1015555). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 protein function. 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 RCV003339590 SCV004058267 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-26 criteria provided, single submitter clinical testing The p.Q912R variant (also known as c.2735A>G), located in coding exon 27 of the RB1 gene, results from an A to G substitution at nucleotide position 2735. The glutamine at codon 912 is replaced by arginine, an amino acid with highly similar 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 RCV001314437 SCV004821732 uncertain significance Retinoblastoma 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces glutamine with arginine at codon 912 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.

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