NM_000289.6(PFKM):c.1918A>G (p.Ile640Val) AND Glycogen storage disease, type VII

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 8, 2023
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:: RCV002651312.4

Allele description [Variation Report for NM_000289.6(PFKM):c.1918A>G (p.Ile640Val)]

NM_000289.6(PFKM):c.1918A>G (p.Ile640Val)

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.1918A>G (p.Ile640Val)

Other names:

p.Ile640Val

HGVS:

NC_000012.12:g.48144083A>G
NG_016199.2:g.43831A>G
NM_000289.6:c.1918A>GMANE SELECT
NM_001166686.2:c.2131A>G
NM_001166687.2:c.1918A>G
NM_001166688.2:c.1918A>G
NM_001354735.1:c.2227A>G
NM_001354736.1:c.2227A>G
NM_001354737.1:c.2131A>G
NM_001354738.1:c.2131A>G
NM_001354739.1:c.2131A>G
NM_001354740.1:c.2062A>G
NM_001354741.2:c.1942A>G
NM_001354742.2:c.1918A>G
NM_001354743.2:c.1918A>G
NM_001354744.2:c.1918A>G
NM_001354745.2:c.1831A>G
NM_001354746.2:c.1792A>G
NM_001354747.2:c.1768A>G
NM_001354748.2:c.1768A>G
NM_001363619.2:c.1825A>G
NP_000280.1:p.Ile640Val
NP_001160158.1:p.Ile711Val
NP_001160159.1:p.Ile640Val
NP_001160160.1:p.Ile640Val
NP_001341664.1:p.Ile743Val
NP_001341665.1:p.Ile743Val
NP_001341666.1:p.Ile711Val
NP_001341667.1:p.Ile711Val
NP_001341668.1:p.Ile711Val
NP_001341669.1:p.Ile688Val
NP_001341670.1:p.Ile648Val
NP_001341671.1:p.Ile640Val
NP_001341672.1:p.Ile640Val
NP_001341673.1:p.Ile640Val
NP_001341674.1:p.Ile611Val
NP_001341675.1:p.Ile598Val
NP_001341676.1:p.Ile590Val
NP_001341677.1:p.Ile590Val
NP_001350548.1:p.Ile609Val
LRG_1177t1:c.1918A>G
LRG_1177:g.43831A>G
LRG_1177p1:p.Ile640Val
NC_000012.11:g.48537866A>G
NR_148954.2:n.2221A>G
NR_148955.1:n.2991A>G
NR_148956.2:n.2147A>G
NR_148957.2:n.2376A>G
NR_148958.2:n.2124A>G
NR_148959.2:n.2050A>G

Protein change:

I590V

Molecular consequence:

NM_000289.6:c.1918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001166686.2:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001166687.2:c.1918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001166688.2:c.1918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354735.1:c.2227A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354736.1:c.2227A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354737.1:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354738.1:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354739.1:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354740.1:c.2062A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354741.2:c.1942A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354742.2:c.1918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354743.2:c.1918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354744.2:c.1918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354745.2:c.1831A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354746.2:c.1792A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354747.2:c.1768A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354748.2:c.1768A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363619.2:c.1825A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148954.2:n.2221A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148955.1:n.2991A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148956.2:n.2147A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148957.2:n.2376A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148958.2:n.2124A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148959.2:n.2050A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003518176	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004235755	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003518176

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 19, 2022)

germline

clinical testing

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

SCV004235755

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 8, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003518176.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 640 of the PFKM protein (p.Ile640Val). This variant is present in population databases (rs142495522, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PFKM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV004235755.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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