NM_005609.4(PYGM):c.1A>C (p.Met1Leu) AND Glycogen storage disease, type V

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Aug 2, 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:: RCV000144425.13

Allele description [Variation Report for NM_005609.4(PYGM):c.1A>C (p.Met1Leu)]

NM_005609.4(PYGM):c.1A>C (p.Met1Leu)

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>C (p.Met1Leu)

HGVS:

NC_000011.10:g.64759898T>G
NG_013018.1:g.5818A>C
NM_001164716.1:c.1A>C
NM_005609.4:c.1A>CMANE SELECT
NP_001158188.1:p.Met1Leu
NP_005600.1:p.Met1Leu
NC_000011.9:g.64527370T>G
NM_005609.2:c.1A>C

Protein change:

M1L; MET1GLY

Links:

OMIM: 608455.0004; dbSNP: rs267606993

NCBI 1000 Genomes Browser:

rs267606993

Molecular consequence:

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

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

Recent activity

Clear Turn Off Turn On

TRN-GTT3-1 tRNA-Asn (anticodon GTT) 3-1 [Homo sapiens]
TRN-GTT3-1 tRNA-Asn (anticodon GTT) 3-1 [Homo sapiens]
Gene ID:100189323

Gene
Profile neighbors for GEO Profiles (Select 132529318) (200)
GEO Profiles
189[geneid] (1024)
ClinVar
Arterial occlusion
Arterial occlusion

MedGen

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022549	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000189480	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no classification provided	not provided	unknown	not provided
SCV002019578	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 26, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003440488	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 2, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7951262, 9506549, 25740218, 28967462, 28492532

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

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

An A-to-C substitution involving the translation initiation codon in a patient with myophosphorylase deficiency (McArdle's disease).

Tsujino S, Rubin LA, Shanske S, DiMauro S.

Hum Mutat. 1994;4(1):73-5. No abstract available.

PubMed [citation]

PMID:: 7951262

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000022549.4

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

Description

In a 36-year-old woman who had been diagnosed with scleroderma at age 33 but who was also found to have myophosphorylase deficiency (GSD5; 232600), Tsujino et al. (1994) identified an A-to-C transversion (ATG to CTG), which abolished the translation initiation codon of the PYGM gene. The patient was a compound heterozygote with a common nonsense mutation, R50X (608455.0001).

#	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 ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000189480.2

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

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

From Revvity Omics, Revvity, SCV002019578.4

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003440488.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the PYGM mRNA. The next in-frame methionine is located at codon 92. Disruption of the initiator codon has been observed in individual(s) with McArdle‚Äôs disease (PMID: 7951262, 9506549, 25740218, 28967462). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 156341).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine