ClinVar Miner

Submissions for variant NM_000151.4(G6PC1):c.229T>C (p.Trp77Arg) (rs104894566)

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
Counsyl RCV000012781 SCV000220994 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2014-12-29 criteria provided, single submitter literature only
Invitae RCV000012781 SCV001201510 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2020-04-18 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 77 of the G6PC protein (p.Trp77Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with GSD1a (PMID: 29374762, 23352793, 16435186, 11916325). ClinVar contains an entry for this variant (Variation ID: 12001). This variant has been reported to affect G6PC protein function (PMID:11739393, 10738525). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000012781 SCV001774622 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2021-08-02 criteria provided, single submitter clinical testing Variant summary: G6PC c.229T>C (p.Trp77Arg) results in a non-conservative amino acid change located in the phosphatidic acid phosphate type 2/haloperoxidase domain (IPR000326) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251312 control chromosomes. c.229T>C has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (example, Chevalier-Porst_1996, Terzioglu_2001, Miltenberger-Miltenyi_2005, Eminoglu_2013, Quackenbush_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal G6P'ase enzyme activity in vitro in an experimental system of COS-7 cells transfected with mutant constructs (example, Bruni_1999). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000012781 SCV000033021 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 1996-05-01 no assertion criteria provided literature only

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.