NM_000289.6(PFKM):c.116G>C (p.Arg39Pro) AND Glycogen storage disease, type VII

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Mar 14, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000001213.14

Allele description [Variation Report for NM_000289.6(PFKM):c.116G>C (p.Arg39Pro)]

NM_000289.6(PFKM):c.116G>C (p.Arg39Pro)

Gene:
PFKM:phosphofructokinase, muscle [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.11
Genomic location:
Preferred name:
NM_000289.6(PFKM):c.116G>C (p.Arg39Pro)
HGVS:
  • NC_000012.12:g.48130393G>C
  • NG_016199.2:g.30141G>C
  • NM_000289.6:c.116G>CMANE SELECT
  • NM_001166686.2:c.329G>C
  • NM_001166687.2:c.116G>C
  • NM_001166688.2:c.116G>C
  • NM_001354735.1:c.425G>C
  • NM_001354736.1:c.425G>C
  • NM_001354737.1:c.329G>C
  • NM_001354738.1:c.329G>C
  • NM_001354739.1:c.329G>C
  • NM_001354740.1:c.260G>C
  • NM_001354741.2:c.140G>C
  • NM_001354742.2:c.116G>C
  • NM_001354743.2:c.116G>C
  • NM_001354744.2:c.116G>C
  • NM_001354745.2:c.29G>C
  • NM_001354746.2:c.116G>C
  • NM_001354747.2:c.10-923G>C
  • NM_001354748.2:c.10-923G>C
  • NM_001363619.2:c.116G>C
  • NP_000280.1:p.Arg39Pro
  • NP_001160158.1:p.Arg110Pro
  • NP_001160159.1:p.Arg39Pro
  • NP_001160160.1:p.Arg39Pro
  • NP_001341664.1:p.Arg142Pro
  • NP_001341665.1:p.Arg142Pro
  • NP_001341666.1:p.Arg110Pro
  • NP_001341667.1:p.Arg110Pro
  • NP_001341668.1:p.Arg110Pro
  • NP_001341669.1:p.Arg87Pro
  • NP_001341670.1:p.Arg47Pro
  • NP_001341671.1:p.Arg39Pro
  • NP_001341672.1:p.Arg39Pro
  • NP_001341673.1:p.Arg39Pro
  • NP_001341674.1:p.Arg10Pro
  • NP_001341675.1:p.Arg39Pro
  • NP_001350548.1:p.Arg39Pro
  • LRG_1177t1:c.116G>C
  • LRG_1177:g.30141G>C
  • LRG_1177p1:p.Arg39Pro
  • NC_000012.11:g.48524176G>C
  • NM_000289.5:c.116G>C
  • NR_148954.2:n.167G>C
  • NR_148955.1:n.937G>C
  • NR_148957.2:n.167G>C
  • NR_148958.2:n.167G>C
Protein change:
R10P; ARG39PRO
Links:
OMIM: 610681.0003; dbSNP: rs121918193
NCBI 1000 Genomes Browser:
rs121918193
Molecular consequence:
  • NM_001354747.2:c.10-923G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354748.2:c.10-923G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000289.6:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166686.2:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166687.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166688.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354735.1:c.425G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354736.1:c.425G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354737.1:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354738.1:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354739.1:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354740.1:c.260G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354741.2:c.140G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354742.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354743.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354744.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354745.2:c.29G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354746.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363619.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148954.2:n.167G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148955.1:n.937G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148957.2:n.167G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148958.2:n.167G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Glycogen storage disease, type VII (GSD7)
Synonyms:
GSD VII; Glycogen storage disease type 7; Muscle phosphofructokinase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009295; MedGen: C0017926; Orphanet: 371; OMIM: 232800

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000021363OMIM
no assertion criteria provided
Pathogenic
(Jan 1, 1998)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

SCV001416143Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Sep 12, 2023)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002091066Natera, Inc.
no assertion criteria provided
Likely pathogenic
(Aug 7, 2020)
germlineclinical testing

SCV004203963Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 14, 2024)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency.

Tsujino S, Servidei S, Tonin P, Shanske S, Azan G, DiMauro S.

Am J Hum Genet. 1994 May;54(5):812-9.

PubMed [citation]
PMID:
7513946
PMCID:
PMC1918246

Combined defects of muscle phosphofructokinase and AMP deaminase in a child with myoglobinuria.

Bruno C, Minetti C, Shanske S, Morreale G, Bado M, Cordone G, DiMauro S.

Neurology. 1998 Jan;50(1):296-8.

PubMed [citation]
PMID:
9443500
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000021363.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In an Italian patient with GSD VII (GSD7; 232800), born of consanguineous parents, Tsujino et al. (1994) identified a homozygous 116G-C transversion in the PFKM gene, resulting in an arg39-to-pro (R39P) substitution. The proband was a 35-year-old man who had complained since adolescence of exercise intolerance, exercise-related myalgia, and cramps, with a few episodes of myoglobinuria after intense exercise. He had first been seen by an internist for mild jaundice.

Bruno et al. (1998) described a 14-year-old boy with exercise-related myalgia and cramps who had had several episodes of myoglobinuria since early childhood. An episode at 2 years of age had caused acute renal failure. Histochemical and biochemical analysis of muscle showed a combined defect of phosphofructokinase and adenosine monophosphate deaminase-1 (AMPD1; 102770). DNA analysis showed that the patient was homozygous for the PFKM R39P substitution and also homozygous for a common mutation found in AMP deaminase deficiency (102770.0001); the latter mutation is found in homozygous state in about 2% of muscle biopsies.

Another pathogenic mutation in the PFKM gene has been described in the same codon (R39L; 610681.0006) (Sherman et al., 1994).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001416143.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This missense change has been observed in individual(s) with glycogen storage disease (PMID: 7513946, 9443500). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 39 of the PFKM protein (p.Arg39Pro). ClinVar contains an entry for this variant (Variation ID: 1154). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg39 amino acid residue in PFKM. Other variant(s) that disrupt this residue have been observed in individuals with PFKM-related conditions (PMID: 8037209, 27066546), which suggests that this may be a clinically significant amino acid residue. 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 PFKM protein function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV002091066.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004203963.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024