ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1325G>C (p.Gly442Ala)

gnomAD frequency: 0.00001  dbSNP: rs1370947947
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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 RCV000691816 SCV000819609 uncertain significance Retinoblastoma 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 442 of the RB1 protein (p.Gly442Ala). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 570851). 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 with a negative 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 RCV001011037 SCV001171315 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-10 criteria provided, single submitter clinical testing The p.G442A variant (also known as c.1325G>C), located in coding exon 13 of the RB1 gene, results from a G to C substitution at nucleotide position 1325. The glycine at codon 442 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238180 SCV002009260 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing

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