Submissions for variant NM_000292.3(PHKA2):c.2746C>T (p.Arg916Trp)

dbSNP: rs1569297427

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000728027	SCV000855547	pathogenic	not provided	2017-07-12	criteria provided, single submitter	clinical testing
Invitae	RCV000810740	SCV000950973	likely pathogenic	Glycogen storage disease IXa1	2020-10-07	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in several individuals affected with glycogen storage disease IX (PMID: 17689125, 28627441, 21646031). ClinVar contains an entry for this variant (Variation ID: 593082). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 916 of the PHKA2 protein (p.Arg916Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000810740	SCV001190284	likely pathogenic	Glycogen storage disease IXa1	2019-08-12	criteria provided, single submitter	clinical testing
Centre for Inherited Metabolic Diseases, Karolinska University Hospital	RCV000810740	SCV002577751	likely pathogenic	Glycogen storage disease IXa1	2022-10-07	criteria provided, single submitter	clinical testing