ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1472T>A (p.Leu491His)

dbSNP: rs587778848
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000695948 SCV000824489 uncertain significance Retinoblastoma 2018-04-05 criteria provided, single submitter clinical testing This sequence change replaces leucine with histidine at codon 491 of the RB1 protein (p.Leu491His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RB1-related disease. 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. 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 RCV003163199 SCV003854418 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-12 criteria provided, single submitter clinical testing The p.L491H variant (also known as c.1472T>A), located in coding exon 16 of the RB1 gene, results from a T to A substitution at nucleotide position 1472. The leucine at codon 491 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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.

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.