NM_004281.3(BAG3):c.211C>T (p.Arg71Trp) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 20, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000456156.6

Allele description [Variation Report for NM_004281.3(BAG3):c.211C>T (p.Arg71Trp)]

NM_004281.3(BAG3):c.211C>T (p.Arg71Trp)

Gene:
BAG3:BAG cochaperone 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q26.11
Genomic location:
Preferred name:
NM_004281.3(BAG3):c.211C>T (p.Arg71Trp)
HGVS:
  • NC_000010.11:g.119669881C>T
  • NG_016125.1:g.23512C>T
  • NM_004281.3:c.211C>T
  • NP_004272.2:p.Arg71Trp
  • LRG_742t1:c.211C>T
  • LRG_742:g.23512C>T
  • LRG_742p1:p.Arg71Trp
  • NC_000010.10:g.121429393C>T
  • O95817:p.Arg71Trp
Protein change:
R71W; ARG71TRP
Links:
UniProtKB: O95817#VAR_065479; OMIM: 603883.0003; dbSNP: rs387906874
NCBI 1000 Genomes Browser:
rs387906874
Molecular consequence:
  • NM_004281.3:c.211C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Myofibrillar myopathy, BAG3-related (MFM6)
Synonyms:
MYOPATHY, MYOFIBRILLAR, 6
Identifiers:
MONDO: MONDO:0013061; MedGen: C2751831; Orphanet: 199340; OMIM: 612954
Name:
Dilated cardiomyopathy 1HH (CMD1HH)
Identifiers:
MONDO: MONDO:0013479; MedGen: C3151293; Orphanet: 154; OMIM: 613881

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000550833Invitaecriteria provided, single submitter
Uncertain significance
(Oct 20, 2020)
germlineclinical testing

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

SCV000894521Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Uncertain significance
(Oct 31, 2018)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]
PMID:
28166811
PMCID:
PMC5295186

Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.

Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Z├╝chner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE.

Am J Hum Genet. 2011 Mar 11;88(3):273-82. doi: 10.1016/j.ajhg.2011.01.016. Epub 2011 Feb 25.

PubMed [citation]
PMID:
21353195
PMCID:
PMC3059419
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000550833.6

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

Description

This sequence change replaces arginine with tryptophan at codon 71 of the BAG3 protein (p.Arg71Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs387906874, ExAC 0.06%) and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals with dilated cardiomyopathy (PMID: 21353195, 30012837). However, in one individual another variant was also identified in TTN, which suggests that this c.211C>T variant may not be the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 30396). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Fulgent Genetics,Fulgent Genetics, SCV000894521.1

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

Last Updated: Jul 29, 2021

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