Submissions for variant NM_000151.4(G6PC1):c.724C>T (p.Gln242Ter)

gnomAD frequency: 0.00001  dbSNP: rs80356485

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000239641	SCV001163789	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA		criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000239641	SCV001194047	likely pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2019-12-20	criteria provided, single submitter	clinical testing	NM_000151.3(G6PC):c.724C>T(Q242*) is classified as likely pathogenic in the context of glycogen storage disease type Ia. Sources cited for classification include the following: 12373566, 19762333, 10834516, 7573034 and 23046672. Classification of NM_000151.3(G6PC):c.724C>T(Q242*) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000239641	SCV001339196	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2020-03-30	criteria provided, single submitter	clinical testing	Variant summary: G6PC c.724C>T (p.Gln242X) 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 1.2e-05 in 251396 control chromosomes (gnomAD). c.724C>T has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (Lei_1995, Calderaro_2012, Matern_2002). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000239641	SCV001440388	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2019-01-01	criteria provided, single submitter	clinical testing	This variant was identified as compound heterozygous.
Invitae	RCV000239641	SCV002510567	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2023-09-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln242*) in the G6PC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 116 amino acid(s) of the G6PC protein. This variant is present in population databases (rs80356485, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with G6PC-related conditions (PMID: 7573034). ClinVar contains an entry for this variant (Variation ID: 21061). 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, Fulgent Genetics	RCV000239641	SCV002798616	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2022-05-23	criteria provided, single submitter	clinical testing
National Center for Biotechnology Information, National Institutes of Health	RCV000239641	SCV000298097	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2016-08-25	no assertion criteria provided	literature only
Natera, Inc.	RCV000239641	SCV002093321	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2017-03-17	no assertion criteria provided	clinical testing