NM_001103.4(ACTN2):c.683T>C (p.Met228Thr) AND Dilated cardiomyopathy 1AA

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000169907.12

Allele description [Variation Report for NM_001103.4(ACTN2):c.683T>C (p.Met228Thr)]

NM_001103.4(ACTN2):c.683T>C (p.Met228Thr)

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.683T>C (p.Met228Thr)

HGVS:

NC_000001.11:g.236731300T>C
NG_009081.2:g.72160T>C
NM_001103.4:c.683T>CMANE SELECT
NM_001278343.2:c.683T>C
NM_001278344.2:c.-139T>C
NP_001094.1:p.Met228Thr
NP_001265272.1:p.Met228Thr
LRG_436t1:c.683T>C
LRG_436:g.72160T>C
LRG_436p1:p.Met228Thr
NC_000001.10:g.236894600T>C
NG_009081.1:g.49831T>C
NM_001103.2:c.683T>C
P35609:p.Met228Thr

Protein change:

M228T; MET228THR

Links:

UniProtKB: P35609#VAR_074292; OMIM: 102573.0007; dbSNP: rs786205144

NCBI 1000 Genomes Browser:

rs786205144

Molecular consequence:

NM_001278344.2:c.-139T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001103.4:c.683T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001278343.2:c.683T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1AA (CMD1AA)
Synonyms:: CARDIOMYOPATHY, DILATED, 1AA, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION; CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 23, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION
Identifiers:: MONDO: MONDO:0012808; MedGen: C2677338; Orphanet: 154; OMIM: 612158

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222241	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000222241

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2014)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Novel α-actinin 2 variant associated with familial hypertrophic cardiomyopathy and juvenile atrial arrhythmias: a massively parallel sequencing study.

Girolami F, Iascone M, Tomberli B, Bardi S, Benelli M, Marseglia G, Pescucci C, Pezzoli L, Sana ME, Basso C, Marziliano N, Merlini PA, Fornaro A, Cecchi F, Torricelli F, Olivotto I.

Circ Cardiovasc Genet. 2014 Dec;7(6):741-50. doi: 10.1161/CIRCGENETICS.113.000486. Epub 2014 Aug 30.

PubMed [citation]

PMID:: 25173926

Details of each submission

From OMIM, SCV000222241.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 11 affected members of a large 4-generation Italian family with clinically heterogeneous cardiomyopathic disease comprising variable combinations of asymmetric left ventricular hypertrophy consistent with hypertrophic cardiomyopathy (CMH23; see 612158) as well as early-onset supraventricular arrhythmias and AV block, and regional left ventricular noncompaction, Girolami et al. (2014) identified heterozygosity for a c.683T-C transition (c.683T-C, NM_001103.2) in the ACTN2 gene, resulting in a met228-to-thr (M228T) substitution at a conserved residue within the actin-binding domain. The mutation, which segregated fully with disease in the family, was not found in 570 control alleles.

#	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		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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