Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001390823 | SCV001592674 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 122 of the G6PC protein (p.Gly122Asp). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects G6PC function (PMID: 11739393). 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. ClinVar contains an entry for this variant (Variation ID: 1076798). This missense change has been observed in individual(s) with glycogen storage disease type Ia (PMID: 10748407, 11196115, 15151508). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs759982943, gnomAD 0.02%). |
Juno Genomics, |
RCV001390823 | SCV005418262 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | criteria provided, single submitter | clinical testing | PM2_Supporting+PM3_Strong+PP4+PP3_Moderate | |
3billion | RCV001390823 | SCV005905043 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-10-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.79 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.85 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001076798). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 10748407). A different missense change at the same codon (p.Gly122Val) has been reported to be associated with G6PC1 related disorder (ClinVar ID: VCV001682499). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
Natera, |
RCV001390823 | SCV002093303 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2021-08-18 | no assertion criteria provided | clinical testing |