NM_004281.4(BAG3):c.612del (p.Tyr205fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 26, 2023
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:: RCV003774628.2

Allele description [Variation Report for NM_004281.4(BAG3):c.612del (p.Tyr205fs)]

NM_004281.4(BAG3):c.612del (p.Tyr205fs)

Gene:

BAG3:BAG cochaperone 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q26.11

Genomic location:

Preferred name:

NM_004281.4(BAG3):c.612del (p.Tyr205fs)

HGVS:

NC_000010.11:g.119672359del
NG_016125.1:g.25990del
NM_004281.4:c.612delMANE SELECT
NP_004272.2:p.Tyr205fs
LRG_742t1:c.608del
LRG_742:g.25990del
NC_000010.10:g.121431867del
NC_000010.10:g.121431871del
NM_004281.3:c.608delG

Protein change:

Y205fs

Links:

dbSNP: rs2134065084

NCBI 1000 Genomes Browser:

rs2134065084

Molecular consequence:

NM_004281.4:c.612del - 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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LOC132718021 [Ruditapes philippinarum]
LOC132718021 [Ruditapes philippinarum]
Gene ID:132718021

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004594507	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 26, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34213952, 21353195, 25008357, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004594507

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 26, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pathogenic Variants Associated With Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis.

Seidel F, Holtgrewe M, Al-Wakeel-Marquard N, Opgen-Rhein B, Dartsch J, Herbst C, Beule D, Pickardt T, Klingel K, Messroghli D, Berger F, Schubert S, Kühnisch J, Klaassen S.

Circ Genom Precis Med. 2021 Aug;14(4):e003250. doi: 10.1161/CIRCGEN.120.003250. Epub 2021 Jul 2.

PubMed [citation]

PMID:: 34213952
PMCID:: PMC8373449

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, Züchner 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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004594507.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1675064). This variant is also known as c.608delG . This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 34213952). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr205Thrfs*6) in the BAG3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BAG3 are known to be pathogenic (PMID: 21353195, 25008357).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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