NM_005609.4(PYGM):c.2082C>A (p.Asp694Glu) AND Glycogen storage disease, type V

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 15, 2020
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:: RCV001267843.2

Allele description [Variation Report for NM_005609.4(PYGM):c.2082C>A (p.Asp694Glu)]

NM_005609.4(PYGM):c.2082C>A (p.Asp694Glu)

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.2082C>A (p.Asp694Glu)

HGVS:

NC_000011.10:g.64750471G>T
NG_013018.1:g.15245C>A
NM_001164716.1:c.1818C>A
NM_005609.4:c.2082C>AMANE SELECT
NP_001158188.1:p.Asp606Glu
NP_005600.1:p.Asp694Glu
NC_000011.9:g.64517943G>T
NM_005609.2:c.2082C>A

Protein change:

D606E

Links:

dbSNP: rs773543072

NCBI 1000 Genomes Browser:

rs773543072

Molecular consequence:

NM_001164716.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005609.4:c.2082C>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

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
SCV001443154	Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 15, 2020)	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

SCV001443154

Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 15, 2020)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
Ashkenazi Jewish	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene.

Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T.

Hum Mutat. 2015 Jul;36(7):669-78. doi: 10.1002/humu.22806. Epub 2015 Jun 3. Review.

PubMed [citation]

PMID:: 25914343

Details of each submission

From Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center, SCV001443154.1

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

Description

The patient is a 28-year-old Ashkenazi Jewish woman who presents with recurrent rhabdomyolysis for 3 years, characterized with exercise intolerance, global muscle weakness, myalgia, arthralgias, and elevated serum creatine kinase

Repeated rhabdomyolysis, myalgia, myoglobinuria

Description

The c.2082C>A variant in PYGM Gene results in the substitution of amino acid residue ASP694 in the glycogen phosphorylase catalytic domain in coding exon 17 (NM_005609.2), which is a hot spot exon for PYGM mutations (Muman Mutat.2015 July;36(7):669-78. The variant is predicted to be deleterious and damaging to the protein function by Provean and SIFT respectively. Additionally, in vitro, functional biochemical studies revealed that this variant is associated with the loss of muscle glycogen phosphorylase activity. In summary, the Asp694Glu variant meets ACMG criteria to be classified as likely pathogenic (Richards et al 2015).

#	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		not provided	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jul 8, 2022

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