ClinVar Miner

Submissions for variant NM_000289.6(PFKM):c.237+1G>A (rs202143236)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare 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.
Counsyl RCV000169670 SCV000487030 pathogenic Glycogen storage disease, type VII 2016-10-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000169670 SCV000893298 likely pathogenic Glycogen storage disease, type VII 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000169670 SCV000937925 pathogenic Glycogen storage disease, type VII 2018-12-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the PFKM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs202143236, ExAC 0.01%). This variant has been observed in several individuals affected with phosphofructokinase (PFK) deficiency and has been observed to segregate with PFK deficiency in a family (PMID: 8037209, 8444874, 28779239). ClinVar contains an entry for this variant (Variation ID: 189239). Experimental studies have shown that this nucleotide change led to skipping of the preceding exon (sometimes called exon 5 in the literature) in mRNA derived from cells of an affected individual (PMID: 8444874). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PFKM are known to be pathogenic (PMID: 7825568, 8037209). For these reasons, this variant has been classified as Pathogenic.
Yale Center for Mendelian Genomics,Yale University RCV000662285 SCV000784613 likely pathogenic Rhabdomyolysis 2017-08-05 no assertion criteria provided literature only

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