Hypertrophic cardiomyopathy - teen and adult

Gene: TTR

Green List (high evidence)

TTR (transthyretin)
EnsemblGeneIds (GRCh38): ENSG00000118271
EnsemblGeneIds (GRCh37): ENSG00000118271
OMIM: 176300, Gene2Phenotype
TTR is in 13 panels

5 reviews

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

Green List (high evidence)

On CGGL Royal Brompton diagnostic panel. Associated with Hereditary amyloidosis, which is phenocopy of HCM, patients can present with LVH, therefore appropriate for overlapping phenotypes
Created: 18 Sep 2019, 12:56 p.m. | Last Modified: 18 Sep 2019, 12:56 p.m.
Panel Version: 1.74

Phenotypes
Amyloidosis, hereditary, transthyretin-related OMIM 105210

Publications

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

Rebecca Whittington (South West GLH)

I don't know

Amyloidosis, hereditary, transthyretin-related (105210 )
Created: 25 Mar 2019, 4:30 p.m.
29567486 /28369730: HCM phenocopy. OMIM 105210 - hereditary, transthyretin-related Amyloidosis: cardiomyopathy associated with phenotype. Few DM variants on HGMD associated with cardiomyopathy, HCM only are VUS. 28635949: specific cardiac variants in this gene.
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

Anna de Burca (Genomics England Curator)

Comment on list classification: Promoted to green following discussion with NHS GMS cardiology specialist group. Cardiac amyloidosis is associated with thickening of the ventricular wall which can resemble hypertrophic cardiomyopathy.
Created: 4 Feb 2019, 7:19 a.m.

Ellen McDonagh (Genomics England Curator)

I don't know

The 'treatable' tag has been added due to new therapies available that target this gene. Inotersen is an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), developed and approved by NICE for the treatment of hereditary transthyretin amyloidosis (hATTR) (PMID: 30120737, https://www.nice.org.uk/guidance/hst9/chapter/1-Recommendations). Patisiran is a small interfering RNA (siRNA) molecule that targets the transthyretin gene (TTR) messenger mRNA (mRNA), to suppress both mutant and wild-type amyloid transthyretin (ATTR) protein production. This drug has been approved by NHSE for treatment of transthyretin-mediated amyloidosis (https://www.bbc.co.uk/news/health-48907976).
Created: 9 Jul 2019, 12:36 p.m. | Last Modified: 9 Jul 2019, 12:36 p.m.
Panel Version: 1.55
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.
Comment on list classification: Promoted from Red to Amber due to new review and discussion with the NHSE GMS Cardiology specialist group.
Created: 17 Jan 2019, 5:14 p.m.

Publications

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Green List (high evidence)

pathogenic variants in this gene cause Hereditary TTR amyloidosis. Affected individuals can present with left ventricular hypertrophy (LVH) that can mimic HCM. Recent study (PMID:28475415) found pathogenic varaint in this gene in 0.6% individuals in HCM cohort (n=697)
Created: 17 Jan 2019, 5:06 p.m.
TTR mutations cause amyloidosis which can manifest as polyneuropathy and / or cardiac amyloidosis (can be misdiagnosed as HCM). 3-4% of black Africans have p.Val142Ile mutation, which can cause cardiomyopathy at >65 years of age. Damy et al. 2015 suggest ~11% of black African HCM patients (>65 years) may have TTR mutation. Other rarer mutations throughout the gene.
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
  • Expert Review Green
  • Wessex and West Midlands GLH
  • Expert list
  • Emory Genetics Laboratory
Phenotypes
  • Cardiac amyloidosis
Tags
treatable
OMIM
176300
Clinvar variants
Variants in TTR
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

9 Jul 2019, Gel status: 3

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: TTR were set to 28475415; 16115295; 16194874; 26537620; 1626570; 1570831

9 Jul 2019, Gel status: 3

Added Tag

Ellen McDonagh (Genomics England Curator)

Tag treatable tag was added to gene: TTR.

21 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to TTR.

20 Feb 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to TTR. Rating Changed from Green List (high evidence) to Green List (high evidence)

4 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Anna de Burca (Genomics England Curator)

Gene: ttr has been classified as Green List (High Evidence).

4 Feb 2019, Gel status: 2

Set Phenotypes

Anna de Burca (Genomics England Curator)

Phenotypes for gene: TTR were changed from syndromic HCM to Cardiac amyloidosis

4 Feb 2019, Gel status: 2

Set Phenotypes

Anna de Burca (Genomics England Curator)

Phenotypes for gene: TTR were changed from syndromic HCM to Cardiac amyloidosis

17 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: ttr has been classified as Amber List (Moderate Evidence).

17 Jan 2019, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: TTR were set to

17 Jan 2019, Gel status: 1

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source Wessex and West Midlands GLH was added to TTR. Mode of inheritance for gene TTR was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

TTR was added to Hypertrophic Cardiomyopathypanel. Sources: Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

TTR was added to Hypertrophic Cardiomyopathypanel. Sources: Emory Genetics Laboratory