Submissions for variant NM_000127.3(EXT1):c.1016G>A (p.Gly339Asp)

dbSNP: rs119103288

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000002604	SCV000930988	pathogenic	Multiple congenital exostosis	2020-11-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change abolishes heparan sulfate biosynthesis and disrupts the activity of the EXT1/EXT2 protein complex (PMID: 10639137, 9620772). This variant has been observed in several individuals affected with hereditary multiple osteochondromatosis (PMID: 9326317, 23439489, Invitae). ClinVar contains an entry for this variant (Variation ID: 2498). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 339 of the EXT1 protein (p.Gly339Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
CeGaT Center for Human Genetics Tuebingen	RCV003311634	SCV004010795	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	EXT1: PM1, PM2, PM5, PS4:Moderate, PP1, PP3, PP4, PS3:Supporting
OMIM	RCV001003501	SCV000022762	pathogenic	Exostoses, multiple, type 1	1998-06-01	no assertion criteria provided	literature only