NM_004281.4(BAG3):c.1321A>G (p.Asn441Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 30, 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:: RCV001050142.6

Allele description [Variation Report for NM_004281.4(BAG3):c.1321A>G (p.Asn441Asp)]

NM_004281.4(BAG3):c.1321A>G (p.Asn441Asp)

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.1321A>G (p.Asn441Asp)

HGVS:

NC_000010.11:g.119676875A>G
NG_016125.1:g.30506A>G
NM_004281.4:c.1321A>GMANE SELECT
NP_004272.2:p.Asn441Asp
NP_004272.2:p.Asn441Asp
LRG_742t1:c.1321A>G
LRG_742:g.30506A>G
LRG_742p1:p.Asn441Asp
NC_000010.10:g.121436387A>G
NM_004281.3:c.1321A>G

Protein change:

N441D

Links:

dbSNP: rs201181493

NCBI 1000 Genomes Browser:

rs201181493

Molecular consequence:

NM_004281.4:c.1321A>G - 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

Recent activity

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PREDICTED: Actinidia eriantha ABC transporter G family member 1-like (LOC1307778...
PREDICTED: Actinidia eriantha ABC transporter G family member 1-like (LOC130777815), transcript variant X4, mRNA
gi|2526847751|ref|XM_057636247.1|

Nucleotide
ubiquitin carboxyl-terminal hydrolase 15 isoform 8 [Homo sapiens]
ubiquitin carboxyl-terminal hydrolase 15 isoform 8 [Homo sapiens]
gi|1189398124|ref|NP_001338092.1|

Protein
zinc finger protein 558 isoform X1 [Homo sapiens]
zinc finger protein 558 isoform X1 [Homo sapiens]
gi|1370474518|ref|XP_024307154.1|

Protein
PREDICTED: Mus musculus OCIA domain containing 1 (Ociad1), transcript variant X1...
PREDICTED: Mus musculus OCIA domain containing 1 (Ociad1), transcript variant X13, misc_RNA
gi|1907165895|ref|XR_001784740.3|

Nucleotide
PREDICTED: Homo sapiens zinc finger protein 558 (ZNF558), transcript variant X3,...
PREDICTED: Homo sapiens zinc finger protein 558 (ZNF558), transcript variant X3, mRNA
gi|2217319566|ref|XM_047438268.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001214238	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 30, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214238

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 30, 2024)

germline

clinical testing

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

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

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, SCV001214238.5

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

Description

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 441 of the BAG3 protein (p.Asn441Asp). This variant is present in population databases (rs201181493, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 191612). 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: Oct 13, 2024

ClinVar

Relating variation to medicine