NM_005609.4(PYGM):c.1A>G (p.Met1Val) AND Glycogen storage disease, type V

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Nov 26, 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:: RCV000002399.16

Allele description [Variation Report for NM_005609.4(PYGM):c.1A>G (p.Met1Val)]

NM_005609.4(PYGM):c.1A>G (p.Met1Val)

Gene:

PYGM:glycogen phosphorylase, muscle associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_005609.4(PYGM):c.1A>G (p.Met1Val)

HGVS:

NC_000011.10:g.64759898T>C
NG_013018.1:g.5818A>G
NM_001164716.1:c.1A>G
NM_005609.4:c.1A>GMANE SELECT
NP_001158188.1:p.Met1Val
NP_005600.1:p.Met1Val
NC_000011.9:g.64527370T>C
NM_005609.2:c.1A>G

Protein change:

M1V; MET1VAL

Links:

OMIM: 608455.0012; dbSNP: rs267606993

NCBI 1000 Genomes Browser:

rs267606993

Molecular consequence:

NM_001164716.1:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_005609.4:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001164716.1:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005609.4:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Glycogen storage disease, type V (GSD5)
Synonyms:: Glycogen storage disease type 5; GSD 5; McArdle disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009293; MedGen: C0017924; Orphanet: 368; OMIM: 232600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022557	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1998)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000485450	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Dec 15, 2015)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19670320, 21802952, 25740218, 9506549 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV002238798	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9506549, 25740218, 28967462, 28492532
SCV002579025	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004171070	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 26, 2023)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Permanent muscle weakness in McArdle disease.

Nadaj-Pakleza AA, Vincitorio CM, Laforêt P, Eymard B, Dion E, Teijeira S, Vietez I, Jeanpierre M, Navarro C, Stojkovic T.

Muscle Nerve. 2009 Sep;40(3):350-7. doi: 10.1002/mus.21351.

PubMed [citation]

PMID:: 19670320

Molecular and clinical study of McArdle's disease in a cohort of 123 European patients. Identification of 20 novel mutations.

Vieitez I, Teijeira S, Fernandez JM, San Millan B, Miranda S, Ortolano S, Louis S, Laforet P, Navarro C.

Neuromuscul Disord. 2011 Dec;21(12):817-23. doi: 10.1016/j.nmd.2011.07.002. Epub 2011 Jul 29.

PubMed [citation]

PMID:: 21802952

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000022557.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a Turkish patient with McArdle disease (GSD5; 232600), Vorgerd et al. (1998) found homozygosity for an A-to-G transition within the initiation codon of the PYGM gene, resulting in a met1-to-val (M1V) substitution. (See also 608455.0004.)

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

From Counsyl, SCV000485450.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002238798.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2309). Disruption of the initiator codon has been observed in individual(s) with McArdle disease (PMID: 9506549, 25740218, 28967462). This variant is present in population databases (rs267606993, gnomAD 0.004%). This sequence change affects the initiator methionine of the PYGM mRNA. The next in-frame methionine is located at codon 92.

#	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 MGZ Medical Genetics Center, SCV002579025.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV004171070.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	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	inherited	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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