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NM_004281.4(BAG3):c.652C>T (p.Arg218Trp) AND Dilated cardiomyopathy 1HH

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 2011
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000032660.10

Allele description [Variation Report for NM_004281.4(BAG3):c.652C>T (p.Arg218Trp)]

NM_004281.4(BAG3):c.652C>T (p.Arg218Trp)

Gene:
BAG3:BAG cochaperone 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q26.11
Genomic location:
Preferred name:
NM_004281.4(BAG3):c.652C>T (p.Arg218Trp)
HGVS:
  • NC_000010.11:g.119672399C>T
  • NG_016125.1:g.26030C>T
  • NM_004281.4:c.652C>TMANE SELECT
  • NP_004272.2:p.Arg218Trp
  • NP_004272.2:p.Arg218Trp
  • LRG_742t1:c.652C>T
  • LRG_742:g.26030C>T
  • LRG_742p1:p.Arg218Trp
  • NC_000010.10:g.121431911C>T
  • NM_004281.3:c.652C>T
  • O95817:p.Arg218Trp
Protein change:
R218W; ARG218TRP
Links:
UniProtKB: O95817#VAR_066781; OMIM: 603883.0007; dbSNP: rs397514506
NCBI 1000 Genomes Browser:
rs397514506
Molecular consequence:
  • NM_004281.4:c.652C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dilated cardiomyopathy 1HH (CMD1HH)
Identifiers:
MONDO: MONDO:0013479; MedGen: C3151293; Orphanet: 154; OMIM: 613881

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000056423OMIM
no assertion criteria provided
Pathogenic
(Dec 1, 2011) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly and enhance sensitivity to apoptosis in cardiomyocytes.

Arimura T, Ishikawa T, Nunoda S, Kawai S, Kimura A.

Hum Mutat. 2011 Dec;32(12):1481-91. doi: 10.1002/humu.21603. Epub 2011 Sep 29.

PubMed [citation]
PMID:
21898660

Details of each submission

From OMIM, SCV000056423.2

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

Description

In a 76-year-old Japanese man who developed dilated cardiomyopathy at age 73 years (CMD1HH; 613881), Arimura et al. (2011) identified heterozygosity for a 652C-T transition in exon 3 of the BAG3 gene, resulting in an arg218-to-trp (R218W) substitution at a highly conserved residue. The patient had 3 affected sisters, 2 of whom had died suddenly; neither of their deceased parents was known to be affected. DNA was not analyzed from any of these family members. Transfection studies in neonatal rat cardiomyocytes (NRCs) demonstrated that wildtype BAG3 had a striated pattern of assembly and colocalized with the Z-disc markers alpha-actinin (see 102575) and desmin (125660), whereas the R218W mutant did not show a striated pattern, and Z-disc assembly as represented by localization of alpha-actinin and desmin was impaired. TUNEL assay in NRCs and quantification of apoptosis in H9c2 cells both indicated that the R218W mutant increased susceptibility to stress-induced apoptosis compared to wildtype.

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

Last Updated: Oct 26, 2024