Hypertrophic cardiomyopathy - teen and adult

Gene: FLNC

Green List (high evidence)

FLNC (filamin C)
EnsemblGeneIds (GRCh38): ENSG00000128591
EnsemblGeneIds (GRCh37): ENSG00000128591
OMIM: 102565, Gene2Phenotype
FLNC is in 9 panels

6 reviews

James Eden (Manchester)

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

Ivone Leong (Genomics England Curator)

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

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

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

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

Rebecca Whittington (South West GLH)

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

Ellen McDonagh (Genomics England Curator)

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.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • South West GLH
  • Wessex and West Midlands GLH
Tags
watchlist
OMIM
102565
Clinvar variants
Variants in FLNC
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

12 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

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

4 Mar 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

4 Mar 2019, Gel status: 2

Added Tag

Ellen McDonagh (Genomics England Curator)

Tag watchlist tag was added to gene: FLNC.

4 Mar 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

21 Feb 2019, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to FLNC.

17 Jan 2019, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: FLNC were set to

17 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

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 FLNC. Mode of inheritance for gene FLNC was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

11 Feb 2016, Gel status: 0

Approved Gene

Caroline Wright (Genomics England Curator)

This proposed gene was validated and added to this panel

6 Jan 2016, Gel status: 0

Created

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

FLNC was created by OxfordGenetics

6 Jan 2016, Gel status: 0

Added New Source

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

FLNC was added to Hypertrophic Cardiomyopathypanel. Sources: Oxford Medical Genetics Laboratory