NM_004281.4(BAG3):c.881G>A (p.Arg294His) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 19, 2024
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:: RCV001048342.6

Allele description [Variation Report for NM_004281.4(BAG3):c.881G>A (p.Arg294His)]

NM_004281.4(BAG3):c.881G>A (p.Arg294His)

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.881G>A (p.Arg294His)

HGVS:

NC_000010.11:g.119672628G>A
NG_016125.1:g.26259G>A
NM_004281.4:c.881G>AMANE SELECT
NP_004272.2:p.Arg294His
NP_004272.2:p.Arg294His
LRG_742t1:c.881G>A
LRG_742:g.26259G>A
LRG_742p1:p.Arg294His
NC_000010.10:g.121432140G>A
NM_004281.3:c.881G>A

Protein change:

R294H

Links:

dbSNP: rs151335530

NCBI 1000 Genomes Browser:

rs151335530

Molecular consequence:

NM_004281.4:c.881G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Cladophora sericea partial 18S rRNA gene, specimen voucher WELT: A033180, isolat...
Cladophora sericea partial 18S rRNA gene, specimen voucher WELT: A033180, isolate B47
gi|1052254270|emb|LT607378.1|

Nucleotide
Mus musculus otopetrin 3 (Otop3), transcript variant 1, mRNA
Mus musculus otopetrin 3 (Otop3), transcript variant 1, mRNA
gi|153791406|ref|NM_027132.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001212342	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31568572, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001212342

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 2024)

germline

clinical testing

PubMed (2)
[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

Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3.

Kühnisch J, Herbst C, Al-Wakeel-Marquard N, Dartsch J, Holtgrewe M, Baban A, Mearini G, Hardt J, Kolokotronis K, Gerull B, Carrier L, Beule D, Schubert S, Messroghli D, Degener F, Berger F, Klaassen S.

Clin Genet. 2019 Dec;96(6):549-559. doi: 10.1111/cge.13645. Epub 2019 Oct 22.

PubMed [citation]

PMID:: 31568572

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001212342.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 294 of the BAG3 protein (p.Arg294His). This variant is present in population databases (rs151335530, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of BAG3-related conditions (PMID: 31568572; Invitae). ClinVar contains an entry for this variant (Variation ID: 386339). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BAG3 protein function with a negative predictive value of 80%. 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.

#	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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