Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673256 | SCV000798438 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2018-03-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000673256 | SCV001222587 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 156 of the G6PC protein (p.Trp156Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with glycogen storage disease type Ia (PMID: 10612834, 28397058). ClinVar contains an entry for this variant (Variation ID: 557154). 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 95%. Experimental studies have shown that this missense change affects G6PC function (PMID: 11739393). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673256 | SCV003934316 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-05-22 | criteria provided, single submitter | clinical testing | Variant summary: G6PC1 c.467G>T (p.Trp156Leu) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Phosphatidic acid phosphatase type 2/haloperoxidase (IPR000326) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251492 control chromosomes. c.467G>T has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (Peeks_2017, Haring_2022). 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, finding that the variant results in <5% of normal phosphohydrolase activity. The following publications have been ascertained in the context of this evaluation (PMID: 11739393, 28397058, 35811762). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Natera, |
RCV000673256 | SCV001463400 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2020-09-16 | no assertion criteria provided | clinical testing |