ClinVar Miner

Submissions for variant NM_000127.3(EXT1):c.840G>C (p.Arg280Ser)

dbSNP: rs1563659325
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 RCV000699208 SCV000827908 pathogenic Multiple congenital exostosis 2018-03-01 criteria provided, single submitter clinical testing This variant has been reported in individuals affected with hereditary multiple osteochondromatosis (PMID: 9521425, Invitae). For these reasons, this variant has been classified as Pathogenic. A different missense substitution at this codon (p.Arg280Gly) has been determined to be pathogenic (PMID: 9463333). This suggests that the arginine residue is critical for EXT1 protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies have shown that this missense changes leads to a loss of heparan sulfate biosynthesis (PMID: 11391482). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 280 of the EXT1 protein (p.Arg280Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine.
GeneDx RCV003126909 SCV003803403 likely pathogenic not provided 2022-08-09 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging loss-of-function impact (Cheung et al., 2001); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9521425, 11391482)

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.