ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.634C>A (p.Leu212Met)

gnomAD frequency: 0.00001  dbSNP: rs147085238
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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 RCV001057563 SCV001222062 uncertain significance Retinoblastoma 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 212 of the RB1 protein (p.Leu212Met). 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: 852857). 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 with a positive predictive value of 80%. 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 RCV002365719 SCV002657963 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-11 criteria provided, single submitter clinical testing The p.L212M variant (also known as c.634C>A), located in coding exon 7 of the RB1 gene, results from a C to A substitution at nucleotide position 634. The leucine at codon 212 is replaced by methionine, 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.
GeneDx RCV004773270 SCV005385181 uncertain significance not provided 2024-01-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23516486)

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