Hypertrophic cardiomyopathy

Gene: FLNC

As a result of watchlist tag audit the watchlist tag was removed from FLNC- this is now a green gene with sufficient evidence/review

Created: 13 Jan 2020, 3:29 p.m. | Last Modified: 13 Jan 2020, 3:29 p.m.

Panel Version: 2.1

I don't know

Gene not currently tested on Manchester cardiac gene panel. 142 variants listed on HGMD (accessed 19/09/2019). ClinGen Knowledge Base: definitive association with myofibrillar myopathy 5 (accessed 19/09/2019).

Created: 19 Sep 2019, 10:05 a.m. | Last Modified: 19 Sep 2019, 10:05 a.m.

Panel Version: 1.74

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

Phenotypes
Cardiomyopathy, familial hypertrophic, 26; Cardiomyopathy, familial restrictive 5 (617047); Myopathy, distal, 4 (614065); Myopathy, myofibrillar, 5 (609524)

Publications

• 28356264

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.

Created: 2 Dec 2019, 11:26 a.m. | Last Modified: 2 Dec 2019, 11:26 a.m.

Panel Version: 1.81

Comment on list classification: Promoted from amber to green based on evidence provided by expert reviews.

Created: 12 Sep 2019, 12:59 p.m. | Last Modified: 12 Sep 2019, 12:59 p.m.

Panel Version: 1.74

Green List (high evidence)

On Royal Brompton diagnostic panel, and pathogenic variants reported in phenotypes of arrythmogenic cardiomyopathy with fibrosis (LOF). Strong evidence of LVH association in literature. On basis of clinical overlap, this should be on HCM panels.

Created: 5 Sep 2019, 3:57 p.m. | Last Modified: 5 Sep 2019, 3:57 p.m.

Panel Version: 1.56

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

Phenotypes
arrythmogenic cardiomyopathy; Cardiomyopathy, familial hypertrophic, 26; Cardiomyopathy, familial restrictive 5; Myopathy, myofibrillar, 5

Publications

• 30681346
• 28356264
• 25351925

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

Green List (high evidence)

Cardiomyopathy, familial hypertrophic, 26 (102565)

Created: 25 Mar 2019, 4:30 p.m.

28369730: Strong evidence, but relatively high frequency of rare variants in population (3.2%). Further characterisation required. 28356264 Gomez 2016 (Circ Cardiovasc Genet. 2017;10:e001584. DOI: 10.1161/CIRCGENETICS.116.001584.) : 6 LP variants in 7 patients. Classification based on ACMG and segregation.

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

Comment on list classification: After discussion at the NHSE GMS Cardiology Specialist Group meeting call on 25th January 2019, this gene should be kept Amber and the 'watchlist' tag added for emerging phenotype data.

Created: 4 Mar 2019, 8:54 p.m.

Comment on list classification: Promoted this gene from Red to Amber for discussion with the NHS GMS Cardiology specialist group.

Created: 17 Jan 2019, 5:11 p.m.

I don't know

Amber gene. For discussion. High background rate of missense variants in reference popualtions in this gene; therefore rare missense variants detected in patients are .are generally uninterpretable and classified as VUS. Heterozygous LOF variants well-established and quite frequent in DCM however we have also found putative LOF variants in HCM patients although these are rare. Another gene where we need more data...

Created: 17 Jan 2019, 5:06 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• Publications supporting role of this gene in HCM - PMID:25351925
• PMID:28356264
• Publications questioning role of this gene in HCM - PMID:30411535

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