Hypertrophic cardiomyopathy - teen and adult

Gene: ACTN2

Amber List (moderate evidence)

ACTN2 (actinin alpha 2)
EnsemblGeneIds (GRCh38): ENSG00000077522
EnsemblGeneIds (GRCh37): ENSG00000077522
OMIM: 102573, Gene2Phenotype
ACTN2 is in 7 panels

5 reviews

James Eden (Manchester)

I don't know

Possible rare cause of HCM. Not currently tested on Manchester HCM panel.
Created: 27 Sep 2019, 1:12 p.m. | Last Modified: 27 Sep 2019, 1:12 p.m.
Panel Version: 1.74

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cardiomyopathy, dilated, 1AA, with or without LVNC 612158; Cardiomyopathy, hypertrophic, 23, with or without LVNC 612158

Publications

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

I don't know

On current CGGL Royal Brompton diagnostic panel, but only VUs reported so far. some limited evidence of LVH phenotype associated, so appropriate for HCm panel due to overlapping phenotype. Listed as definite cardiomyopathy gene by ClinGen.
Created: 18 Sep 2019, 1:07 p.m. | Last Modified: 18 Sep 2019, 1:07 p.m.
Panel Version: 1.74

Variants in this GENE are reported as part of current diagnostic practice

Rebecca Whittington (South West GLH)

I don't know

Cardiomyopathy, hypertrophic, 23, with or without LVNC (612158)
Created: 25 Mar 2019, 4:30 p.m.
Reported to segregate in relatively large pedigrees, but LOD score <3. Moderate evidence: 28082330. Classified as a core HCM gene: 29567486
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

I don't know

Amber gene. For discussion. A very small number of missense variant (n=2) have been show to segreate with atypical cardiac phenotypes-not specifically HCM. ClinGen have labelled this an intrinsic cardiomyoapthy gene. Missense variants (other than the 2 reported in the literature with segregation) are generally uninterpretable and so classified as VUS. In previous case vs control analyses (Walsh et al PMID -27532257) we did not detect a burden of rare missense variants in this gene in cases (HCM or DCM) compared to reference cohorts. However we have emerging evidence from our cohort that heterozygous LOF(including large scale deletions and duplications) variants in this gene may be pathogenic. At present not a Green gene but perhaps worthy of further investigation.
Created: 17 Jan 2019, 5:06 p.m.
Only two variants (p.Ala119Thr and p.Met228Thr) described with significant cosegregation evidence. Phenotypes inc. HCM, LVNC, and arrhythmias. Incomplete penetrance described.
Created: 6 Jan 2016, 5:11 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • South West GLH
  • London South GLH
  • Wessex and West Midlands GLH
  • Expert list
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
OMIM
102573
Clinvar variants
Variants in ACTN2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Feb 2019, Gel status: 2

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to ACTN2. Mode of inheritance for gene ACTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to ACTN2.

17 Jan 2019, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: ACTN2 were set to

17 Jan 2019, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

Source Wessex and West Midlands GLH was added to ACTN2.

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

ACTN2 was added to Hypertrophic Cardiomyopathypanel. Sources: Expert list

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene ACTN2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

ACTN2 was added to Hypertrophic Cardiomyopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ACTN2 was added to Hypertrophic Cardiomyopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN