NM_000256.3(MYBPC3):c.2827C>T (p.Arg943Ter) AND Familial hypertrophic cardiomyopathy 4

Clinical significance:Pathogenic (Last evaluated: Aug 1, 2010)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000030699.7

Allele description [Variation Report for NM_000256.3(MYBPC3):c.2827C>T (p.Arg943Ter)]

NM_000256.3(MYBPC3):c.2827C>T (p.Arg943Ter)

Gene:
MYBPC3:myosin binding protein C, cardiac [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p11.2
Genomic location:
Preferred name:
NM_000256.3(MYBPC3):c.2827C>T (p.Arg943Ter)
HGVS:
  • NC_000011.10:g.47335120G>A
  • NG_007667.1:g.22583C>T
  • NM_000256.3:c.2827C>T
  • NP_000247.2:p.Arg943Ter
  • LRG_386t1:c.2827C>T
  • LRG_386:g.22583C>T
  • LRG_386p1:p.Arg943Ter
  • NC_000011.9:g.47356671G>A
  • c.2827C>T
  • p.Arg943X
  • p.R943*:CGA>TGA
Protein change:
R943*; ARG943TER
Links:
OMIM: 600958.0023; dbSNP: 387907267
NCBI 1000 Genomes Browser:
rs387907267
Molecular consequence:
  • NM_000256.3:c.2827C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Familial hypertrophic cardiomyopathy 4 (CMH4)
Identifiers:
MedGen: C1861862; OMIM: 115197

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000053360OMIMno assertion criteria providedPathogenic
(Aug 1, 2010)
germlineliterature only

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

SCV000219774Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository (COGR)no assertion criteria provided
(Clinical testing)
Pathogenicgermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only, clinical testing

Citations

PubMed

Unexpected myopathy associated with a mutation in MYBPC3 and misplacement of the cardiac myosin binding protein C.

Tajsharghi H, Leren TP, Abdul-Hussein S, Tulinius M, Brunvand L, Dahl HM, Oldfors A.

J Med Genet. 2010 Aug;47(8):575-7. doi: 10.1136/jmg.2009.072710. Epub 2009 Oct 26.

PubMed [citation]
PMID:
19858127

Two cases of severe neonatal hypertrophic cardiomyopathy caused by compound heterozygous mutations in the MYBPC3 gene.

Lekanne Deprez RH, Muurling-Vlietman JJ, Hruda J, Baars MJ, Wijnaendts LC, Stolte-Dijkstra I, Alders M, van Hagen JM.

J Med Genet. 2006 Oct;43(10):829-32. Epub 2006 May 5.

PubMed [citation]
PMID:
16679492
PMCID:
PMC2563166

Details of each submission

From OMIM, SCV000053360.1

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

Description

In a female infant with fatal cardiomyopathy (CMH4; 115197) who also had evidence of skeletal myopathy, Tajsharghi et al. (2010) identified homozygosity for a 2827C-T transition, resulting in an arg943-to-ter (R943X) substitution in the MYBPC3 gene. Skeletal muscle biopsy at 2 months of age showed pronounced myopathic changes with numerous small fibers, which all expressed slow/beta-cardiac myosin heavy chain protein (MYH7; 160760). Electron microscopy revealed disorganization of the sarcomeres and partial depletion of thick filaments in the small fibers; immunohistochemical staining showed the presence of cardiac MYBPC in the small abnormal fibers. RT-PCR and sequencing demonstrated the mutation in transcripts of skeletal muscle. Tajsharghi et al. (2010) noted that cardiac MYBPC is not normally expressed in skeletal muscle, and stated that the reason for the ectopic expression of cardiac MYBPC remained unknown. The R943X mutation had previously been identified in compound heterozygosity with other truncating MYBPC3 mutations in 2 unrelated Dutch infants with fatal hypertrophic cardiomyopathy (Lekanne Deprez et al., 2006); skeletal myopathy was not mentioned in that report.

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

From Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository (COGR), SCV000219774.1

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

Last Updated: Jun 23, 2016