Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000507730 | SCV000603763 | pathogenic | not specified | 2016-09-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000012784 | SCV000776251 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 38 of the G6PC protein (p.Asp38Val). This variant is present in population databases (rs104894565, gnomAD 0.002%). This missense change has been observed in individuals with glycogen storage disease type Ia (PMID: 8733042, 9359038, 10070617, 10834516, 11310582). ClinVar contains an entry for this variant (Variation ID: 12004). 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 G6PC protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects G6PC function (PMID: 9359038, 11739393). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000012784 | SCV000917379 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2018-02-01 | criteria provided, single submitter | clinical testing | Variant summary: G6PC c.113A>T (p.Asp38Val) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246454 control chromosomes in gnomAD and literature. This frequency is not significantly higher than expected for a pathogenic variant in G6PC causing Glycogen Storage Disease Type Ia (8.1e-06 vs 1.70E-03), allowing no conclusion about variant significance. c.113A>T has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia, including one confirmed homozygote (Chevalier-Porst_1996, Stroppiano_1999, Reis_2001). 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 abolished enzymatic activity (Chevalier-Porst_1996). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000012784 | SCV001163777 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | criteria provided, single submitter | clinical testing | ||
Gene |
RCV002243637 | SCV002513755 | pathogenic | not provided | 2022-05-12 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on enzyme activity (Parvari et al., 1997); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11739393, 28074886, 34258141, 8733042, 9359038) |
Mayo Clinic Laboratories, |
RCV002243637 | SCV004228176 | pathogenic | not provided | 2023-03-27 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2, PM3, PS3, PS4_moderate |
OMIM | RCV000012784 | SCV000033024 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 1996-05-01 | no assertion criteria provided | literature only | |
Counsyl | RCV000012784 | SCV001132392 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2018-06-25 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000012784 | SCV002093291 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2017-03-17 | no assertion criteria provided | clinical testing |