ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1345G>A (p.Gly449Arg)

dbSNP: rs1131690851
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
Ambry Genetics RCV000492212 SCV000580779 pathogenic Hereditary cancer-predisposing syndrome 2012-10-02 criteria provided, single submitter clinical testing Co-segregation data for this variant is currently unavailable. This variant has not been detected in conjunction with a pathogenic mutation to date. Allele frequency data in population-based cohorts is not currently available. This amino acid position is completely conserved on sequence alignment.This alteration is predicted to be deleterious with a score of 0.010 (conservation: 1.79)
Labcorp Genetics (formerly Invitae), Labcorp RCV000698759 SCV000827444 pathogenic Retinoblastoma 2020-02-17 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported to be de novo in individuals affected with bilateral retinoblastoma (PMID: 28193182, Invitae) and has been observed to segregate with retinoblastoma in a family (PMID: 17096365). The variant is also known as g.76442G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 428669). This sequence change replaces glycine with arginine at codon 449 of the RB1 protein (p.Gly449Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine RCV000698759 SCV005046111 likely pathogenic Retinoblastoma 2024-05-20 criteria provided, single submitter clinical testing Case and Pedigree Information: BILATERAL CASES:1, UNILATERAL CASES:0, TOTAL CASES:1, PEDIGREES:1. ACMG Codes Applied:PM1, PM2

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.