ClinVar Miner

Submissions for variant NM_000289.6(PFKM):c.237+1G>A

gnomAD frequency: 0.00006  dbSNP: rs202143236
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000169670 SCV000221205 pathogenic Glycogen storage disease, type VII 2014-12-15 criteria provided, single submitter clinical testing The 237+1G>A variant in PFKM has been previously identified in one homozygous patient with glycogen storage disease 7 and was found to segregate with disease in an affected homozygous relative (Raben 1993). This variant is located in the 5' splice region and computational tools do suggest an impact to splicing. In summary, this variant meets our criteria for pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV000169670 SCV000893298 pathogenic Glycogen storage disease, type VII 2022-04-06 criteria provided, single submitter clinical testing
Invitae RCV000169670 SCV000937925 pathogenic Glycogen storage disease, type VII 2024-01-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the PFKM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs202143236, gnomAD 0.2%). Disruption of this splice site has been observed in individuals with phosphofructokinase deficiency (PMID: 8037209, 8444874, 28779239). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189239). Studies have shown that disruption of this splice site results in skipping of exon 4, but is expected to preserve the integrity of the reading-frame (PMID: 8444874). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000169670 SCV002018765 pathogenic Glycogen storage disease, type VII 2023-11-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000169670 SCV002050182 likely pathogenic Glycogen storage disease, type VII 2020-12-03 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000169670 SCV002060337 pathogenic Glycogen storage disease, type VII 2021-11-08 criteria provided, single submitter clinical testing NM_001166686.1(PFKM):c.450+1G>A is a canonical splice variant classified as pathogenic in the context of glycogen storage disease type VII. c.450+1G>A has been observed in cases with relevant disease (PMID: 8037209). Functional assessments of this variant are not available in the literature. c.450+1G>A has been observed in population frequency databases (gnomAD: ASJ 0.24%). In summary, NM_001166686.1(PFKM):c.450+1G>A is a canonical splice variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
GeneDx RCV002243838 SCV002512918 likely pathogenic not provided 2022-04-15 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 28779239, 28627441, 8444874, 25525159, 31589614, 31653659)
Baylor Genetics RCV000169670 SCV004203926 pathogenic Glycogen storage disease, type VII 2023-10-25 criteria provided, single submitter clinical testing
OMIM RCV000169670 SCV000021365 pathogenic Glycogen storage disease, type VII 1997-12-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV000662285 SCV000784613 likely pathogenic Rhabdomyolysis 2017-08-05 no assertion criteria provided literature only
Natera, Inc. RCV000169670 SCV001457676 pathogenic Glycogen storage disease, type VII 2020-09-16 no assertion criteria provided clinical testing

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