Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000670966 | SCV000795896 | uncertain significance | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2017-11-29 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000670966 | SCV002510624 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2021-06-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt G6PC protein function. This variant has been observed in individual(s) with glycogen storage disease (PMID: 9506659). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 555193). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 264 of the G6PC protein (p.Asn264Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. Experimental studies have shown that this variant affects G6PC protein function (PMID: 11739393). |