ClinVar Miner

Submissions for variant NM_000151.4(G6PC1):c.328G>A (p.Glu110Lys) (rs104894567)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000012785 SCV000789384 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2017-02-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000012785 SCV001362494 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2019-11-01 criteria provided, single submitter clinical testing Variant summary: G6PC c.328G>A (p.Glu110Lys) results in a conservative amino acid change located in the Phosphatidic acid phosphatase type 2/haloperoxidase domain (IPR000326) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251416 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in G6PC causing Glycogen Storage Disease Type Ia (6.4e-05 vs 0.0017), allowing no conclusion about variant significance. c.328G>A has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (Chevalier-Porst_1996, YangChou_1999, Trioche_2000, Beegle_2014). These data indicate that the variant is very likely to be associated with disease. Publications also reported that the variant results in less than 10% of normal glucose-6-phosphatase activity (Chevalier-Porst_1996, YangChou_1999, Shieh_2002). One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000012785 SCV001589642 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2020-07-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 110 of the G6PC protein (p.Glu110Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs104894567, ExAC 0.001%). This variant has been observed in individual(s) with glycogen storage disease type 1 (PMID: 18083610, 8733042). ClinVar contains an entry for this variant (Variation ID: 12005). This variant has been reported to affect G6PC protein function (PMID: 21983240, 11739393, 10322403). This variant disrupts the p.Glu110 amino acid residue in G6PC. Other variant(s) that disrupt this residue have been observed in individuals with G6PC-related conditions (PMID: 9359038), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012785 SCV000033025 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 1996-05-01 no assertion criteria provided literature only

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