Submissions for variant NM_000159.4(GCDH):c.1286C>T (p.Thr429Met)

gnomAD frequency: 0.00001  dbSNP: rs745360675

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000673919	SCV000799175	uncertain significance	Glutaric aciduria, type 1	2018-04-12	criteria provided, single submitter	clinical testing
Invitae	RCV000673919	SCV000825736	pathogenic	Glutaric aciduria, type 1	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 429 of the GCDH protein (p.Thr429Met). This variant is present in population databases (rs745360675, gnomAD 0.006%). This missense change has been observed in individual(s) with glutaric aciduria type I (PMID: 9600243, 10699052, 24973495). ClinVar contains an entry for this variant (Variation ID: 557741). 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 GCDH protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GCDH function (PMID: 9600243, 24973495). For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV000673919	SCV000891266	pathogenic	Glutaric aciduria, type 1	2018-10-22	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000673919	SCV004199231	likely pathogenic	Glutaric aciduria, type 1	2024-02-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000673919	SCV002087001	pathogenic	Glutaric aciduria, type 1	2021-03-10	no assertion criteria provided	clinical testing