ClinVar Miner

Submissions for variant NM_000151.4(G6PC1):c.969C>A (p.Tyr323Ter) (rs780226142)

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Total submissions: 5
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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
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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, LabCorp RCV000169104 SCV001363567 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2021-03-08 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. The variant was absent in 251410 control chromosomes (gnomAD). c.969C>A has been reported in the literature in individuals affected with Glycogen Storage Disease Type Ia (Calderaro_2013, Sperb-Ludwig_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000169104 SCV001406031 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2019-09-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the G6PC gene (p.Tyr323*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acids of the G6PC protein. This variant is present in population databases (rs780226142, ExAC 0.001%). This variant has been observed in an individual affected with glycogen storage disease (PMID: 23046672). ClinVar contains an entry for this variant (Variation ID: 188777). This variant disrupts the C-terminus of the G6PC protein. Other variant(s) that disrupt this region (p.Gln347*) have been determined to be pathogenic (PMID: 7573034, 8182131, 8733042, 10070617, 11949931, 28397058). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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