ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1448A>T (p.His483Leu)

dbSNP: rs1948522736
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002044933 SCV002116546 uncertain significance Retinoblastoma 2021-10-04 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. This variant disrupts the p.His483 amino acid residue in RB1. Other variant(s) that disrupt this residue have been observed in individuals with RB1-related conditions (PMID: 11480772, 21538077, 28193182), which suggests that this may be a clinically significant amino acid residue. 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. This missense change has been observed in individual(s) with head and neck cancer (PMID: 24888624). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with leucine at codon 483 of the RB1 protein (p.His483Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine.

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.