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NM_004281.4(BAG3):c.1067dup (p.Pro357fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 23, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003807770.2

Allele description [Variation Report for NM_004281.4(BAG3):c.1067dup (p.Pro357fs)]

NM_004281.4(BAG3):c.1067dup (p.Pro357fs)

Gene:
BAG3:BAG cochaperone 3 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
10q26.11
Genomic location:
Preferred name:
NM_004281.4(BAG3):c.1067dup (p.Pro357fs)
HGVS:
  • NC_000010.11:g.119676621dup
  • NG_016125.1:g.30252dup
  • NM_004281.4:c.1067dupMANE SELECT
  • NP_004272.2:p.Pro357Thrfs
  • NP_004272.2:p.Pro357fs
  • LRG_742t1:c.1067dup
  • LRG_742:g.30252dup
  • LRG_742p1:p.Pro357Thrfs
  • NC_000010.10:g.121436128_121436129insC
  • NC_000010.10:g.121436133dup
  • NM_004281.3:c.1067dup
Protein change:
P357fs
Molecular consequence:
  • NM_004281.4:c.1067dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Myofibrillar myopathy 6
Synonyms:
Myofibrillar myopathy, BAG3-related
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
SCV004591992Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 23, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy.

Janin A, N'Guyen K, Habib G, Dauphin C, Chanavat V, Bouvagnet P, Eschalier R, Streichenberger N, Chevalier P, Millat G.

Clin Genet. 2017 Dec;92(6):616-623. doi: 10.1111/cge.13043. Epub 2017 May 18.

PubMed [citation]
PMID:
28436997

Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study.

Morales A, Kinnamon DD, Jordan E, Platt J, Vatta M, Dorschner MO, Starkey CA, Mead JO, Ai T, Burke W, Gastier-Foster J, Jarvik GP, Rehm HL, Nickerson DA, Hershberger RE; DCM Precision Medicine study of the DCM Consortium.; DCM Consortium institutions and personnel participating in this study: Study Principal Investigator and Co-Investigators,DCM Consortium Clinical Site Principal Investigators and Clinical Site Other Significant Contributors (OSC). The following clinical sites and individuals contributed to the submission of RO 1 H L 128857 as Site Principal Investigators (Site Pl) or as Other Significant Contributors (OSC),Dr. Huggins also served as study co-principal investigator,The following clinical site was added following approval of NHGRI supplemental funding but prior to initiation of enrollment,The following clinical sites were added following study activation..

Circ Genom Precis Med. 2020 Apr;13(2):e002480. doi: 10.1161/CIRCGEN.119.002480. Epub 2020 Mar 11.

PubMed [citation]
PMID:
32160020
PMCID:
PMC8070981
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004591992.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BAG3 protein in which other variant(s) (p.Arg473*) have been determined to be pathogenic (PMID: 28436997, 32160020). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with BAG3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro357Thrfs*4) in the BAG3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 219 amino acid(s) of the BAG3 protein.

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

Last Updated: Sep 29, 2024