Submissions for variant NM_000151.4(G6PC1):c.980_982del (p.Phe327del)

dbSNP: rs80356486

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409898	SCV000486957	likely pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2016-09-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000409898	SCV001338491	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2020-04-02	criteria provided, single submitter	clinical testing	Variant summary: G6PC c.980_982delTCT (p.Phe327del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 4e-06 in 251410 control chromosomes (gnomAD). c.980_982delTCT (p.Phe327del) has been reported in the literature in multiple individuals (both homozygous and compound heterozygous) affected with Glycogen Storage Disease Type Ia (e.g. Lei_1995, Kishnani_2009). These data indicate that the variant is very likely to be associated with disease. In functional studies, the variant was found to have very low or no enzymatic activity (e.g. Lei_1995, Shieh_2002). Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000409898	SCV002510574	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2023-03-29	criteria provided, single submitter	clinical testing	This variant, c.980_982del, results in the deletion of 1 amino acid(s) of the G6PC protein (p.Phe327del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs770928376, gnomAD 0.002%). This variant has been observed in individual(s) with glycogen storage disease (PMID: 7814621, 10834516, 11739393). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1057delTTC or delta F327. ClinVar contains an entry for this variant (Variation ID: 371388). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects G6PC function (PMID: 7814621, 11739393). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000409898	SCV002793720	likely pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2022-05-27	criteria provided, single submitter	clinical testing
National Center for Biotechnology Information, National Institutes of Health	RCV000409898	SCV000298098	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2016-08-25	no assertion criteria provided	literature only
Natera, Inc.	RCV000409898	SCV002093332	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2017-03-17	no assertion criteria provided	clinical testing