NM_004281.4(BAG3):c.1408C>T (p.Pro470Ser) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 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:: RCV001046418.5

Allele description

NM_004281.4(BAG3):c.1408C>T (p.Pro470Ser)

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.1408C>T (p.Pro470Ser)

HGVS:

NC_000010.11:g.119676962C>T
NG_016125.1:g.30593C>T
NM_004281.4:c.1408C>TMANE SELECT
NP_004272.2:p.Pro470Ser
LRG_742t1:c.1408C>T
LRG_742:g.30593C>T
NC_000010.10:g.121436474C>T
NM_004281.3:c.1408C>T

Protein change:

P470S

Links:

dbSNP: rs756020699

NCBI 1000 Genomes Browser:

rs756020699

Molecular consequence:

NM_004281.4:c.1408C>T - 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001210322	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32859500, 30559338, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001210322

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2023)

germline

clinical testing

PubMed (3)
[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

A family with adult-onset myofibrillar myopathy with BAG3 mutation (P470S) presenting with axonal polyneuropathy.

Hamaguchi M, Kokubun N, Inoue M, Komagamine T, Aoki R, Nishino I, Hirata K.

Neuromuscul Disord. 2020 Sep;30(9):727-731. doi: 10.1016/j.nmd.2020.07.012. Epub 2020 Aug 1.

PubMed [citation]

PMID:: 32859500

Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks.

Meister-Broekema M, Freilich R, Jagadeesan C, Rauch JN, Bengoechea R, Motley WW, Kuiper EFE, Minoia M, Furtado GV, van Waarde MAWH, Bird SJ, Rebelo A, Zuchner S, Pytel P, Scherer SS, Morelli FF, Carra S, Weihl CC, Bergink S, Gestwicki JE, Kampinga HH.

Nat Commun. 2018 Dec 17;9(1):5342. doi: 10.1038/s41467-018-07718-5.

PubMed [citation]

PMID:: 30559338
PMCID:: PMC6297355

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001210322.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 470 of the BAG3 protein (p.Pro470Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myofibrillar myopathy (PMID: 30559338, 32859500). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 843736). 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 expected to disrupt BAG3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects BAG3 function (PMID: 30559338). For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 6, 2024

ClinVar

Relating variation to medicine