Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000797174 | SCV000936719 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-08-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val88Phefs*14) in the G6PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). This variant is present in population databases (rs755612674, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with glycogen storage disease (PMID: 9630072, 10604148, 20509832, 24980439). This variant is also known as 341delG. ClinVar contains an entry for this variant (Variation ID: 643470). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV001267228 | SCV001445409 | pathogenic | Inborn genetic diseases | 2017-11-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000797174 | SCV002570515 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-07-25 | criteria provided, single submitter | clinical testing | Variant summary: G6PC c.262delG (p.Val88PhefsX14) 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 classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251466 control chromosomes (gnomAD). c.262delG has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (e.g. Zheng_2014, Liang_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three 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. |
Natera, |
RCV000797174 | SCV002093299 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2017-03-17 | no assertion criteria provided | clinical testing |