ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1334G>A (p.Arg445Gln)

gnomAD frequency: 0.00001  dbSNP: rs747509282
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001236052 SCV001408764 uncertain significance Retinoblastoma 2023-05-17 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 962236). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (rs747509282, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 445 of the RB1 protein (p.Arg445Gln).
Ambry Genetics RCV002379900 SCV002694477 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-12 criteria provided, single submitter clinical testing The p.R445Q variant (also known as c.1334G>A), located in coding exon 14 of the RB1 gene, results from a G to A substitution at nucleotide position 1334. The arginine at codon 445 is replaced by glutamine, an amino acid with highly 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.
All of Us Research Program, National Institutes of Health RCV001236052 SCV004844659 uncertain significance Retinoblastoma 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 445 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has been identified in 1/249104 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.