Submissions for variant NM_000294.3(PHKG2):c.469G>A (p.Glu157Lys)

gnomAD frequency: 0.00001  dbSNP: rs752961445

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000761513	SCV001225250	likely pathogenic	Glycogen storage disease IXc	2023-10-16	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 157 of the PHKG2 protein (p.Glu157Lys). This variant is present in population databases (rs752961445, gnomAD 0.0009%). This missense change has been observed in individuals with clinical features of glycogen storage disease type IXc (GSDIXc) (PMID: 12930917, 25266922; Invitae). ClinVar contains an entry for this variant (Variation ID: 623365). 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 PHKG2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000761513	SCV001984633	uncertain significance	Glycogen storage disease IXc	2020-09-21	criteria provided, single submitter	clinical testing
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	RCV000761513	SCV000891642	likely pathogenic	Glycogen storage disease IXc	2017-12-30	no assertion criteria provided	curation