Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169104 | SCV000220300 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2014-05-08 | criteria provided, single submitter | literature only | |
| Eurofins Ntd Llc |
RCV000726277 | SCV000343386 | pathogenic | not provided | 2016-06-29 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000169104 | SCV001163791 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169104 | SCV001363567 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-10-25 | criteria provided, single submitter | clinical testing | Variant summary: G6PC c.969C>A (p.Tyr323X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been associated with Glycogen Storage Disease in HGMD. The variant was absent in 251410 control chromosomes. c.969C>A has been reported in the literature as a compound heterozygous genotype in individuals affected with Glycogen Storage Disease Type Ia (Calderaro_2013 and Sperb-Ludwig_2019). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. Studies using G6PC-EGFP construct shows undetectable level of protein expression and significantly altered N-linked glycosylatin (Plona_2019) . Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000169104 | SCV001406031 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr323*) in the G6PC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the G6PC protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 23046672). ClinVar contains an entry for this variant (Variation ID: 188777). This variant disrupts a region of the G6PC protein in which other variant(s) (p.Gln347*) have been determined to be pathogenic (PMID: 7573034, 8182131, 8733042, 10070617, 11949931, 28397058). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000169104 | SCV002811000 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-04-20 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000726277 | SCV004228180 | pathogenic | not provided | 2023-03-27 | criteria provided, single submitter | clinical testing | PM2, PM3_supporting, PS3, PVS1_strong |