ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.800C>T (p.Pro267Leu)

gnomAD frequency: 0.00001  dbSNP: rs138484426
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672714 SCV000797848 uncertain significance Non-ketotic hyperglycinemia 2018-02-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000672714 SCV001395430 pathogenic Non-ketotic hyperglycinemia 2023-09-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 267 of the GLDC protein (p.Pro267Leu). This variant is present in population databases (rs138484426, gnomAD 0.01%). This missense change has been observed in individual(s) with nonketotic hyperglycinemia (PMID: 26179960, 28244183; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 556679). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GLDC protein function. This variant disrupts the p.Pro267 amino acid residue in GLDC. Other variant(s) that disrupt this residue have been observed in individuals with GLDC-related conditions (PMID: 27362913), which suggests that this may be a clinically significant amino acid residue.

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.