ClinVar Miner

Submissions for variant NM_000151.4(G6PC):c.1039C>T (p.Gln347Ter) (rs80356487)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000199372 SCV000230856 pathogenic not provided 2015-04-07 criteria provided, single submitter clinical testing
GeneDx RCV000199372 SCV000251525 pathogenic not provided 2017-07-03 criteria provided, single submitter clinical testing The Q347X variant in the G6PC gene has been reported previously in association with autosomal recessive glycogen storage disease type 1a when present in the homozygous state or when in trans with another pathogenic variant (Lei et al., 1994; Kozak et al., 2000; Carlin et al., 2013). Site-directed mutagenesis and transient expression assays in COS1 cells demonstrated a loss of glucose-6-phosphatase activity (Lei et al., 1994). This variant is predicted to cause loss of normal protein function through protein truncation as the last 11 amino acids of the protein are lost. The Q347X variant is observed in 29/66,352 alleles (0.04%) from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). We interpret Q347X as a pathogenic variant.
Counsyl RCV000012780 SCV000485169 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2016-01-05 criteria provided, single submitter clinical testing
Invitae RCV000012780 SCV000776256 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2019-12-23 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the G6PC gene (p.Gln347*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 11 amino acids of the G6PC protein. This variant is present in population databases (rs80356487, ExAC 0.04%). This variant is the second most common cause of glycogen storage disease type 1A in Caucasians (PMID: 7573034, 8182131, 8733042, 10070617, 11949931, 28397058). ClinVar contains an entry for this variant (Variation ID: 12000). Experimental studies have shown that this nonsense change reduces G6PC enzymatic activity (PMID: 8182131). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000012780 SCV000894123 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000012780 SCV000919368 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2017-09-25 criteria provided, single submitter clinical testing Variant summary: The G6PC c.1039C>T (p.Gln347X) variant results in a premature termination codon, predicted to cause a truncated or absent G6PC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 56/276802 control chromosomes at a frequency of 0.0002023, which does not exceed the estimated maximal expected allele frequency of a pathogenic G6PC variant (0.0017321). Multiple publications have cited the variant in affected compound heterozygote and homozygote individuals that had little to none glucose-6-phosphatase activity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV000012780 SCV001163792 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000012780 SCV001194080 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2019-11-12 criteria provided, single submitter clinical testing NM_000151.3(G6PC):c.1039C>T(Q347*) is classified as pathogenic in the context of glycogen storage disease type Ia. Sources cited for classification include the following: PMID 8733042, 10738525, 19815695, 10874313, 24385852, 18449899, 7573034, 10070617 and 8182131. Classification of NM_000151.3(G6PC):c.1039C>T(Q347*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000012780 SCV000033020 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 1994-05-01 no assertion criteria provided literature only
GeneReviews RCV000012780 SCV000040455 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2016-08-25 no assertion criteria provided literature only
Natera Inc RCV001027894 SCV001190617 pathogenic Glycogen storage disease 2019-05-20 no assertion criteria provided clinical testing

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