Submissions for variant NM_000289.6(PFKM):c.1321G>T (p.Glu441Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV002309296	SCV002603107	likely pathogenic	Glycogen storage disease, type VII	2022-03-30	criteria provided, single submitter	clinical testing	NM_001166686.1(PFKM):c.1534G>T(E512*) is expected to be pathogenic in the context of glycogen storage disease type VII. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in PFKM, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Invitae	RCV002309296	SCV004338275	pathogenic	Glycogen storage disease, type VII	2023-11-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu441*) in the PFKM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PFKM are known to be pathogenic (PMID: 7825568, 8037209). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PFKM-related conditions. ClinVar contains an entry for this variant (Variation ID: 1725612). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.