ClinVar Miner

Submissions for variant NM_000151.4(G6PC1):c.883C>T (p.Arg295Cys) (rs104894563)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000012779 SCV000220708 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2014-09-18 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725438 SCV000336926 pathogenic not provided 2015-11-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000012779 SCV000402984 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2017-04-27 criteria provided, single submitter clinical testing The G6PC c.883C>T (p.Arg295Cys) variant was reported in a compound heterozygous state with a second variant in two individuals with glycogen storage disease (GSD) type I and in five alleles from individuals with the disorder (Lei et al. 1993; Lei et al 1995; Stroppiano et al. 1999; Kozak et al. 2000; Matern et al. 2002; Di Rocco et al. 2008). The variant was absent from a total of 14 healthy control individuals but is reported at a frequency of 0.00002 in the Total population of the Exome Aggregation Consortium. Functional studies by Lei et al. (1993) showed that phosphohydrolase activity was abolished in COS1 cells expressing the p.Arg295Cys variant, while research by Shieh et al. (2002) suggested that the p.Arg295Cys variant could cause misfolding and protein degradation. Based on the evidence, the p.Arg295Cys variant is classified as likely pathogenic for glycogen storage disease type I. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000012779 SCV000695633 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2016-07-08 criteria provided, single submitter clinical testing Variant summary: The G6PC c.883C>T (p.Arg295Cys) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 3/121408 control chromosomes at a frequency of 0.0000247, which does not exceed the estimated maximal expected allele frequency of a pathogenic G6PC variant (0.0017321). This variant has been reported in numerous GSD1a patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000012779 SCV000830993 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 295 of the G6PC protein (p.Arg295Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs104894563, ExAC 0.01%). This variant has been observed in individuals affected with glycogen storage disease type la (PMID: 10070617, 12373566, 18083610, 8211187). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.962C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 11999). Experimental studies have shown that this variant abolishes affects phosphohydrolase activity (PMID: 8211187, 11739393). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012779 SCV000033019 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 1993-10-22 no assertion criteria provided literature only

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