ClinVar Miner

Submissions for variant NM_000151.4(G6PC):c.377_378TA[3] (p.Tyr128fs) (rs80356488)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000417779 SCV000228794 pathogenic not provided 2015-02-20 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000012777 SCV000402979 pathogenic Glycogen storage disease type 1A 2017-04-27 criteria provided, single submitter clinical testing The G6PC c.379_380dupTA (p.Tyr128ThrfsTer3) variant, also referred to as c.376_377insTA, causes a frameshift and is predicted to truncate the protein. The p.Tyr128ThrfsTer3 variant was first identified by Lei et al. (1993) in a homozygous state in an individual whose liver biopsy contained no detectable G6Pase activity. Since then, the variant has been identified in several affected Hispanic individuals in both the homozygous and compound heterozygous state, and is a known common variant in individuals with glycogen storage disease (GSD) type Ia, accounting for approximately 50% of disease alleles in Hispanic populations (Lei et al. 1995; Rake et al. 2000; Matern et al. 2002; Koeberl et al. 2009; Wang et al. 2013). The variant was also shown to segregate with disease (Lei et al. 1995). Control data are not reported for this variant in these studies, but the variant is reported at a frequency of 0.00115 in the Latino population of the Exome Aggregation Consortium. Transient expression analysis of the p.Tyr128ThrfsTer3 variant showed the variant abolished G6Pase activity (Rake et al. 2000). Based on the collective evidence, the p.Tyr128ThrfsTer3 variant is classified as pathogenic for glycogen storage disease type I. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Counsyl RCV000012777 SCV000485232 likely pathogenic Glycogen storage disease type 1A 2015-12-21 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000417779 SCV000511076 pathogenic not provided 2016-10-24 criteria provided, single submitter clinical testing
Invitae RCV000012777 SCV000827517 pathogenic Glycogen storage disease type 1A 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr128Thrfs*3) in the G6PC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs756356652, ExAC 0.1%). This variant has been reported in several individuals affected with glycogen storage disease type Ia (PMID: 8211187, 28397058, 22899091). ClinVar contains an entry for this variant (Variation ID: 11997). Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012777 SCV000033017 pathogenic Glycogen storage disease type 1A 1995-10-01 no assertion criteria provided literature only
GeneReviews RCV000012777 SCV000040459 pathogenic Glycogen storage disease type 1A 2016-08-25 no assertion criteria provided literature only
National Center for Biotechnology Information, National Institutes of Health RCV000012777 SCV000298095 pathogenic Glycogen storage disease type 1A 2016-08-25 no assertion criteria provided literature only

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