NM_005609.4(PYGM):c.2392T>C (p.Trp798Arg) AND Glycogen storage disease, type V

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 12, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
7 submissions [Details]
Record status:
current
Accession:
RCV000002402.9

Allele description [Variation Report for NM_005609.4(PYGM):c.2392T>C (p.Trp798Arg)]

NM_005609.4(PYGM):c.2392T>C (p.Trp798Arg)

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.2392T>C (p.Trp798Arg)
Other names:
W797R; NM_001164716.1(PYGM):c.2128T>C(p.Trp710Arg); NM_005609.2(PYGM):c.2392T>C(p.Trp798Arg)
HGVS:
  • NC_000011.10:g.64746796A>G
  • NG_007574.1:g.3661T>C
  • NG_013018.1:g.18920T>C
  • NM_001164716.1:c.2128T>C
  • NM_005609.4:c.2392T>CMANE SELECT
  • NP_001158188.1:p.Trp710Arg
  • NP_005600.1:p.Trp798Arg
  • NP_005600.1:p.Trp798Arg
  • LRG_100:g.3661T>C
  • NC_000011.9:g.64514268A>G
  • P11217:p.Trp798Arg
Protein change:
W710R; Trp797Arg
Links:
UniProtKB: P11217#VAR_014015; OMIM: 608455.0015; dbSNP: rs119103258
NCBI 1000 Genomes Browser:
rs119103258
Molecular consequence:
  • NM_001164716.1:c.2128T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005609.4:c.2392T>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000022560OMIMno assertion criteria providedPathogenic
(Jan 1, 2001)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000172201GeneReviewsno assertion criteria providedPathogenic
(Jun 26, 2014)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000677925Counsylcriteria provided, single submitter
Pathogenic
(Jul 29, 2015)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV000803466SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Likely pathogenic
(May 31, 2018)
unknowncuration

PubMed (5)
[See all records that cite these PMIDs]

SCV000893903Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Likely pathogenic
(Oct 31, 2018)
unknownclinical testing

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

SCV001461268Natera, Inc.no assertion criteria providedPathogenic
(Sep 16, 2020)
germlineclinical testing

SCV001580144Invitaecriteria provided, single submitter
Pathogenic
(Jun 12, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing, curation
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Relatively high frequency in Spanish population (12%)germlineyesnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.

Martín MA, Rubio JC, García A, Fernández MA, Campos Y, Krawczak M, Cooper DN, Arenas J.

Clin Genet. 2001 Jan;59(1):48-51.

PubMed [citation]
PMID:
11168025

A proposed molecular diagnostic flowchart for myophosphorylase deficiency (McArdle disease) in blood samples from Spanish patients.

Rubio JC, Garcia-Consuegra I, Nogales-Gadea G, Blazquez A, Cabello A, Lucia A, Andreu AL, Arenas J, Martin MA.

Hum Mutat. 2007 Feb;28(2):203-4.

PubMed [citation]
PMID:
17221871
See all PubMed Citations (12)

Details of each submission

From OMIM, SCV000022560.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Martin et al. (2001) performed mutation analysis on DNA from 54 Spanish patients (40 families) with glycogen storage disease V (GSD5; 232600) and found that 16.5% of patients and 13.7% of mutant alleles had the W797R substitution previously described by Fernandez et al. (2000).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV000172201.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Relatively high frequency in Spanish population (12%)not providednot providednot providedliterature only PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000677925.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From SIB Swiss Institute of Bioinformatics, SCV000803466.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (5)

Description

This variant is interpreted as a Likely Pathogenic, for Glycogen storage disease 5, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Common mutation observed in multiple unrelated patients. (PMID:10590419,29143597,/10681080,14722619). PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:29143597). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Fulgent Genetics,Fulgent Genetics, SCV000893903.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV001461268.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001580144.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces tryptophan with arginine at codon 798 of the PYGM protein (p.Trp798Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is present in population databases (rs119103258, ExAC 0.003%). This missense change has been observed to be homozygous or in combination with another PYGM variant in individuals affected with McArdle disease (PMID: 10590419,30415384,17994553,22250184,10681080). This variant is also known as W797R in the literature. ClinVar contains an entry for this variant (Variation ID: 2312). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 16, 2021

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