Limb-Girdle Muscular Dystrophy and Distal Myopathy
Gene: FLNCEnsemblGeneIds (GRCh38): ENSG00000128591
EnsemblGeneIds (GRCh37): ENSG00000128591
OMIM: 102565, Gene2Phenotype
FLNC is in 12 panels
3 reviews
Bryony Thompson (Royal Melbourne Hospital)
Well-established gene-disease associations. Split by mechanism of disease:
Myofibrillar myopathy - misfolded protein/impaired cross-linking/loss of dimerisation - heterozygous missense/in-frame indels in the ROD2 domain cause hypertrophic cardiomyopathy, restrictive cardiomyopathy, or myofibrillar myopathy (proximal/distal), and truncating variants in the last exon also cause myofibrillar myopathy (proximal/distal).
Dilated cardiomyopathy - loss of function/haploinsufficiency - truncating variants cause dilated cardiomyopathy, arrhythmogenic potential, or distal myopathy (only present in the Ig-like domain 15).
Distal myopathy with posterior leg and anterior hand involvement - toxic gain of function - missense resulting in uncharged amino acids in the actin-binding domain cause distal myopathy (at least 3 variants).Created: 11 May 2022, 3:45 a.m. | Last Modified: 11 May 2022, 3:45 a.m.
Panel Version: 0.14085
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Myofibrillar myopathy MONDO:0018943; Dilated cardiomyopathy MONDO:0005021; distal myopathy with posterior leg and anterior hand involvement MONDO:0013550
Publications
Variants in this GENE are reported as part of current diagnostic practice
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
Comment when marking as ready: Causes a range of conditions affecting muscle, phenotypic overlap.Created: 1 Jul 2020, 7:57 a.m. | Last Modified: 1 Jul 2020, 7:57 a.m.
Panel Version: 0.48
Elena Savva (Victorian Clinical Genetics Services)
Myofibrillar myopathy - LOF
Distal myopathy - GOF
Cardiomyopathy, familial hypertrophic - LOF PTCs
PMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild.
3/4 also presented with arthrogryposis
Sources: Expert listCreated: 1 Jul 2020, 2:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Cardiomyopathy, familial restrictive 5 617047; Myopathy, distal, 4 614065; Myopathy, myofibrillar, 5 609524
Publications
- PMID: 29858533
Mode of pathogenicity
Other
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Green
- Expert Review Green
- Expert list
- Phenotypes
-
- Cardiomyopathy, familial restrictive 5 617047
- Myopathy, distal, 4 614065
- Myopathy, myofibrillar, 5 609524
- OMIM
- 102565
- Clinvar variants
- Variants in FLNC
- Penetrance
- None
- Publications
-
- PMID: 29858533
- Mode of Pathogenicity
- Other
- Panels with this gene
-
- Limb-Girdle Muscular Dystrophy and Distal Myopathy
- Additional findings_Adult
- Arrhythmogenic Cardiomyopathy
- Fetal anomalies
- Additional findings_Paediatric
- Cardiomyopathy_Paediatric
- Arthrogryposis
- Mendeliome
- Dilated Cardiomyopathy
- BabyScreen+ newborn screening
- Transplant Co-Morbidity Superpanel
- Hypertrophic cardiomyopathy_HCM
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: flnc has been classified as Green List (High Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: flnc has been classified as Green List (High Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity
Elena Savva (Victorian Clinical Genetics Services)gene: FLNC was added gene: FLNC was added to Limb Girdle Muscular Dystrophy. Sources: Expert list Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FLNC were set to PMID: 29858533 Phenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5 617047; Myopathy, distal, 4 614065; Myopathy, myofibrillar, 5 609524 Mode of pathogenicity for gene: FLNC was set to Other Review for gene: FLNC was set to GREEN