Submissions for variant NM_000151.4(G6PC1):c.247C>A (p.Arg83Ser)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330449	SCV004039099	likely pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2023-08-02	criteria provided, single submitter	clinical testing	Variant summary: G6PC1 (also known as G6PC) c.247C>A (p.Arg83Ser) results in a non-conservative amino acid change located in the Phosphatidic acid phosphatase type 2/haloperoxidase domain (IPR000326) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 282828 control chromosomes (gnomAD). To our knowledge, no occurrence of c.247C>A in individuals affected with Glycogen Storage Disease Type Ia has been reported. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Lei_1995). In addition, other missense variants in the same residue (R83C, R83H) have been reported in the Human Gene Mutation Database in association with Glycogen Storage Disease Type Ia and classified as pathogenic in our lab. The following publication have been ascertained in the context of this evaluation (PMID: 7744838). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.