NM_005609.4(PYGM):c.2T>C (p.Met1Thr) AND Glycogen storage disease, type V

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 28, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001244574.10

Allele description [Variation Report for NM_005609.4(PYGM):c.2T>C (p.Met1Thr)]

NM_005609.4(PYGM):c.2T>C (p.Met1Thr)

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.2T>C (p.Met1Thr)

HGVS:

NC_000011.10:g.64759897A>G
NG_013018.1:g.5819T>C
NM_001164716.1:c.2T>C
NM_005609.4:c.2T>CMANE SELECT
NP_001158188.1:p.Met1Thr
NP_005600.1:p.Met1Thr
NC_000011.9:g.64527369A>G
NM_005609.3:c.2T>C

Protein change:

M1T

Links:

dbSNP: rs2058423391

NCBI 1000 Genomes Browser:

rs2058423391

Molecular consequence:

NM_001164716.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_005609.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001164716.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005609.4:c.2T>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

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
SCV001417803	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 28, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7951262, 9506549, 25740218, 28492532
SCV002092358	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Oct 30, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001417803

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 28, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002092358

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Oct 30, 2020)

germline

clinical testing

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

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

Mutation analysis in myophosphorylase deficiency (McArdle's disease).

Vorgerd M, Kubisch C, Burwinkel B, Reichmann H, Mortier W, Tettenborn B, Pongratz D, Lindemuth R, Tegenthoff M, Malin JP, Kilimann MW.

Ann Neurol. 1998 Mar;43(3):326-31.

PubMed [citation]

PMID:: 9506549

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001417803.6

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Disruption of the initiator codon has been observed in individuals affected with glycogen storage disease, aka polyglucosan body myopathy (PMID: 7951262, 9506549, 25740218). This variant is not present in population databases (ExAC no frequency). 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 Natera, Inc., SCV002092358.2

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

#	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