ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2758A>G (p.Met920Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002439439 SCV002752158 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-21 criteria provided, single submitter clinical testing The p.M920V variant (also known as c.2758A>G), located in coding exon 27 of the RB1 gene, results from an A to G substitution at nucleotide position 2758. The methionine at codon 920 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003514587 SCV004284799 uncertain significance Retinoblastoma 2023-06-20 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 920 of the RB1 protein (p.Met920Val). 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) 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. ClinVar contains an entry for this variant (Variation ID: 1795629). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%).

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