ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.997C>G (p.Gln333Glu) (rs794726972)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000419557 SCV000224785 uncertain significance not provided 2015-01-27 criteria provided, single submitter clinical testing
GeneDx RCV000419557 SCV000521169 likely pathogenic not provided 2018-11-02 criteria provided, single submitter clinical testing The Q333E missense change in the GCDH gene has been previously reported as disease-causing (Goodman et al., 1998). Q333E is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. It occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The Q333E variant is predicted to be located on the surface of the GCDH gene and to be involved in GCDH homotetramerisation; approximately 20% of missense variants reported in association with GA1 are located on the surface of GCDH, supporting the functional importance of this region of the protein (Schmiesing et al., 2017). In summary, we interpret Q333E as likely pathogenic.
Counsyl RCV000675103 SCV000800645 uncertain significance Glutaric aciduria, type 1 2018-01-02 criteria provided, single submitter clinical testing
Invitae RCV000675103 SCV000955272 uncertain significance Glutaric aciduria, type 1 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 333 of the GCDH protein (p.Gln333Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with glutaric aciduria (PMID: 9711871). ClinVar contains an entry for this variant (Variation ID: 193561). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.