PRKAG2:c.1199C>A (p.Thr400Asn) AND Primary familial hypertrophic cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: May 4, 2012)

Review status:

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000038910.1

Allele description [Variation Report for PRKAG2:c.1199C>A (p.Thr400Asn)]

Gene:
PRKAG2:protein kinase, AMP-activated, gamma 2 non-catalytic subunit [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
PRKAG2:c.1199C>A (p.Thr400Asn)
HGVS:
  • NC_000007.14:g.151568750G>T
  • NG_007486.1:g.313481C>A
  • NM_016203.3:c.1199C>A
  • NP_057287.2:p.Thr400Asn
  • NC_000007.13:g.151265836G>T
  • c.1199C>A
Protein change:
T400N; THR400ASN
Links:
OMIM: 602743.0004; dbSNP: 28938173
NCBI 1000 Genomes Browser:
rs28938173
Molecular consequence:
  • NM_016203.3:c.1199C>A: missense variant [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:
Cardiomyopathy, Hypertrophic, Familial; Hypertrophic cardiomyopathy
Identifiers:
MedGen: C0949658

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000062588Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicineclassified by single submitterprobably pathogenic
(May 4, 2012)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot provided1not providednot providednot providedclinical testing

Citations

PubMed

Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy.

Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE.

J Clin Invest. 2002 Feb;109(3):357-62.

PubMed [citation]
PMID:
11827995
PMCID:
PMC150860

A new mutation in PRKAG2 gene causing hypertrophic cardiomyopathy with conduction system disease and muscular glycogenosis.

LaforĂȘt P, Richard P, Said MA, Romero NB, Lacene E, Leroy JP, Baussan C, Hogrel JY, Lavergne T, Wahbi K, Hainque B, Duboc D.

Neuromuscul Disord. 2006 Mar;16(3):178-82. Epub 2006 Feb 17.

PubMed [citation]
PMID:
16487706
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000062588.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The Thr400Asn variant in PRKAG2 has been reported in 1 individual with LVH and WPW syndrome (Arad 2002). An endomyocardial biopsy showed vacuolization and myocyte disarray was absent, which is consistent with storage cardiomyopathy caused by PRKAG2 variants (Arad 2002). This variant has been identified in 1 Caucasian individual with HCM and WPW tested by our laboratory (this individual's daughter) and was not identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). The low frequency of this variant, along with functional studies in yeast and mice (Arad 2002, Banerjee 2009, Scott 2004), and computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) all support a pathogenic role. In addition, this variant is located within the CBS domain region (amino acids 274-556) where all pathogenic PRKAG2 variants have been identified to date (Oliveira 2003). In summary, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providedassert pathogenicitynot providednot provided1not provided

Last Updated: Jun 20, 2014

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