ClinVar Miner

Submissions for variant NM_000127.2(EXT1):c.1016G>A (p.Gly339Asp) (rs119103288)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000002604 SCV000930988 pathogenic Multiple congenital exostosis 2019-02-22 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). 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). 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). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV001003501 SCV000022762 pathogenic Multiple exostoses type 1 1998-06-01 no assertion criteria provided literature only

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