Submissions for variant NM_000127.3(EXT1):c.1018C>G (p.Arg340Gly)

dbSNP: rs119103290

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001270018	SCV001450441	likely pathogenic	not provided	2019-09-23	criteria provided, single submitter	clinical testing
Invitae	RCV002537726	SCV003440815	pathogenic	Multiple congenital exostosis	2022-06-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg340 amino acid residue in EXT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9521425, 26239617, 26961984). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXT1 protein function. ClinVar contains an entry for this variant (Variation ID: 988576). This missense change has been observed in individual(s) with hereditary multiple osteochondromas, also known as hereditary multiple exostoses (PMID: 28600779, 33726816). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 340 of the EXT1 protein (p.Arg340Gly).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV004527418	SCV005038818	pathogenic	Exostoses, multiple, type 1	2024-03-14	criteria provided, single submitter	clinical testing