ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1922C>A (p.Pro641Gln)

gnomAD frequency: 0.00003  dbSNP: rs1249069450
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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 RCV001955861 SCV002221472 uncertain significance Retinoblastoma 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 641 of the RB1 protein (p.Pro641Gln). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 1444255). 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. 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.
Sema4, Sema4 RCV002258337 SCV002530812 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-18 criteria provided, single submitter curation
Ambry Genetics RCV002258337 SCV002720657 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-05 criteria provided, single submitter clinical testing The p.P641Q variant (also known as c.1922C>A), located in coding exon 19 of the RB1 gene, results from a C to A substitution at nucleotide position 1922. The proline at codon 641 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. 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.

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