ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2639A>C (p.Glu880Ala)

gnomAD frequency: 0.00001  dbSNP: rs1259535894
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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 RCV001362780 SCV001558816 uncertain significance Retinoblastoma 2023-04-12 criteria provided, single submitter clinical testing 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: 1054298). 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). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 880 of the RB1 protein (p.Glu880Ala).
GeneDx RCV002260704 SCV002540353 uncertain significance not provided 2022-01-04 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: 20694007)
Ambry Genetics RCV002432019 SCV002743355 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-22 criteria provided, single submitter clinical testing The p.E880A variant (also known as c.2639A>C), located in coding exon 25 of the RB1 gene, results from an A to C substitution at nucleotide position 2639. The glutamic acid at codon 880 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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