NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 6, 2014
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:: RCV000150148.11

Allele description [Variation Report for NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr)]

NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr)

Gene:

ACTN2:actinin alpha 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr)

HGVS:

NC_000001.11:g.236719007G>A
NG_009081.2:g.59867G>A
NM_001103.4:c.355G>AMANE SELECT
NM_001278343.2:c.355G>A
NM_001278344.2:c.-467G>A
NP_001094.1:p.Ala119Thr
NP_001094.1:p.Ala119Thr
NP_001265272.1:p.Ala119Thr
LRG_436t1:c.355G>A
LRG_436:g.59867G>A
LRG_436p1:p.Ala119Thr
NC_000001.10:g.236882307G>A
NG_009081.1:g.37538G>A
NM_001103.2:c.355G>A
NM_001103.3:c.355G>A
P35609:p.Ala119Thr

Protein change:

A119T; ALA119THR

Links:

UniProtKB: P35609#VAR_071970; OMIM: 102573.0005; dbSNP: rs727502886

NCBI 1000 Genomes Browser:

rs727502886

Molecular consequence:

NM_001278344.2:c.-467G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001103.4:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278343.2:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000197014	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Feb 6, 2014)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20022194, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000197014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Feb 6, 2014)

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	not provided	3	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis.

Chiu C, Bagnall RD, Ingles J, Yeates L, Kennerson M, Donald JA, Jormakka M, Lind JM, Semsarian C.

J Am Coll Cardiol. 2010 Mar 16;55(11):1127-35. doi: 10.1016/j.jacc.2009.11.016.

PubMed [citation]

PMID:: 20022194

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000197014.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Ala119Thr variant in ACTN2 has previously been reported in a large Austral ian family with HCM, segregated with disease in 6 affected relatives including o ne obligate carrier (Chiu 2006). It was absent from large population studies. Th is variant meets our criteria to be classified as pathogenic for HCM based upon segregation studies and absence from controls.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		3	not provided	1	not provided

Last Updated: Mar 5, 2025

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