Submissions for variant NM_207122.2(EXT2):c.1200C>A (p.Phe400Leu)

gnomAD frequency: 0.00003  dbSNP: rs773613001

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001053665	SCV001217938	uncertain significance	Exostoses, multiple, type 2	2023-07-03	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with multiple osteochondromatosis (PMID: 28849184). 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. 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 not expected to disrupt EXT2 protein function. ClinVar contains an entry for this variant (Variation ID: 849654). This variant is also known as c.1299C>A, p.Phe433Leu. This variant is present in population databases (rs773613001, gnomAD 0.1%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 400 of the EXT2 protein (p.Phe400Leu).
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153911	SCV003843485	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing