FLNC

filamin C, the group of Filamins

Basic information

Region (hg38): 7:128830406-128859274

Previous symbols: [ "FLN2" ]

Links

ENSG00000128591 ∙ NCBI:2318 ∙ OMIM:102565 ∙ HGNC:3756 ∙ Uniprot:Q14315 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 10.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000325888.13	ENSP00000327145.8	48	yes	-
ENST00000346177.6	ENSP00000344002.6	47	-	-
ENST00000714183.1	ENSP00000519472.1	47	-	-
ENST00000714184.1	ENSP00000519473.1	46	-	-

Phenotypes

GenCC

Source: genCC

• distal myopathy with posterior leg and anterior hand involvement (Moderate), mode of inheritance: AD
• hypertrophic cardiomyopathy 26 (Moderate), mode of inheritance: AD
• dilated cardiomyopathy (Definitive), mode of inheritance: AD
• dilated cardiomyopathy (Definitive), mode of inheritance: AD
• myofibrillar myopathy (Definitive), mode of inheritance: AD
• heart conduction disease (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 26 (Strong), mode of inheritance: AD
• myofibrillar myopathy 5 (Strong), mode of inheritance: AD
• distal myopathy with posterior leg and anterior hand involvement (Supportive), mode of inheritance: AD
• familial isolated restrictive cardiomyopathy (Supportive), mode of inheritance: AD
• myofibrillar myopathy 5 (Supportive), mode of inheritance: AD
• dilated cardiomyopathy (Definitive), mode of inheritance: AD
• myofibrillar myopathy 5 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic 26 (Cardiomyopthy, familial restrictive 5); Myopathy, distal, 4; Myopathy, myofibrillar, 5	AD	Cardiovascular	Individuals (including with Distal myopathy or Myofibrillar myopathy) have been described with cardiomyopathy, and surveillance (eg, including echocardiography an electrocardiography) may allow early diagnosis and management	Cardiovascular; Musculoskeletal	15929027; 15824355; 19050726; 21620354; 22131542; 22806379; 23109048; 25351925; 26666891

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLNC gene.

• not_provided (5296 variants)
• Hypertrophic_cardiomyopathy_26 (5193 variants)
• Distal_myopathy_with_posterior_leg_and_anterior_hand_involvement (5139 variants)
• Myofibrillar_myopathy_5 (5137 variants)
• Cardiovascular_phenotype (2259 variants)
• not_specified (410 variants)
• Dilated_Cardiomyopathy,_Dominant (172 variants)
• FLNC-related_disorder (150 variants)
• Cardiomyopathy (131 variants)
• Primary_dilated_cardiomyopathy (34 variants)
• Primary_familial_dilated_cardiomyopathy (23 variants)
• Hypertrophic_cardiomyopathy (13 variants)
• Restrictive_cardiomyopathy (7 variants)
• Primary_familial_hypertrophic_cardiomyopathy (5 variants)
• Arrhythmogenic_right_ventricular_cardiomyopathy (4 variants)
• Cardiomyopathy,_familial_restrictive,_5 (3 variants)
• See_cases (3 variants)
• Myofibrillar_myopathy (2 variants)
• Wolff-Parkinson-White_pattern (2 variants)
• Limb-girdle_muscular_dystrophy (2 variants)
• Arrhythmogenic_right_ventricular_dysplasia,_familial,_15 (2 variants)
• Dilated_cardiomyopathy_1A (1 variants)
• Desmin-related_myofibrillar_myopathy (1 variants)
• FLNC-associated_cardiomyopathy (1 variants)
• Distal_myopathy (1 variants)
• Congenital_long_QT_syndrome (1 variants)
• Inborn_genetic_diseases (1 variants)
• Disorder_of_cardiovascular_system (1 variants)
• Two-raphe_bicuspid_aortic_valve (1 variants)
• Asymmetric_septal_hypertrophy (1 variants)
• Nemaline_myopathy (1 variants)
• Asymmetry_of_the_thorax (1 variants)
• Episodic_vomiting (1 variants)
• Tetralogy_of_Fallot (1 variants)
• Patent_foramen_ovale (1 variants)
• Muscle_weakness (1 variants)
• Cardiomyopathy,_familial_restrictive,_1 (1 variants)
• Facial_asymmetry (1 variants)
• Abnormality_of_the_musculature (1 variants)
• Conduction_disorder_of_the_heart (1 variants)
• Cerebellar_ataxia (1 variants)
• Spastic_ataxia (1 variants)
• SUDDEN_INFANT_DEATH_SYNDROME (1 variants)
• Abnormal_ventricular_septum_morphology (1 variants)
• Abnormal_morphology_of_left_ventricular_trabeculae (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLNC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001458.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	3		30	1416	28	1477
missense	12	40	2512	425	12	3001
nonsense	119	27	7			153
start loss						0
frameshift	268	76	12			356
splice donor/acceptor (+/-2bp)	13	97	15			125
Total	415	240	2576	1841	40

Highest pathogenic variant AF is 0.00020144769

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLNC	protein_coding	protein_coding	ENST00000325888	48	28898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125609	0	38	125647	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.79	1369	1.69e+3	0.809	0.000117	17582
Missense in Polyphen		603	860.05	0.70112		9087
Synonymous	-0.679	766	742	1.03	0.0000579	5651
Loss of Function	7.96	18	107	0.169	0.00000543	1284

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000237	0.000235
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000277	0.000273
Finnish	0.00	0.00
European (Non-Finnish)	0.000153	0.000149
Middle Eastern	0.000277	0.000273
South Asian	0.000164	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross- linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.
• Disease: DISEASE: Myopathy, myofibrillar, 5 (MFM5) [MIM:609524]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM5 is characterized by onset in adulthood, clinical features of a limb-girdle myopathy, and focal myofibrillar destruction. {ECO:0000269|PubMed:15929027}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, distal, 4 (MPD4) [MIM:614065]: A slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation. {ECO:0000269|PubMed:21620354}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 26 (CMH26) [MIM:617047]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:25351925}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial restrictive 5 (RCM5) [MIM:617047]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269|PubMed:26666891}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);Salmonella infection - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Focal Adhesion;MAPK Signaling Pathway;Cell-extracellular matrix interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.00661
• rvis_EVS: -3.64
• rvis_percentile_EVS: 0.29

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.908

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: flnca
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: non-functional

Gene ontology

• Biological process: cell junction assembly;muscle fiber development
• Cellular component: cytoplasm;cytosol;cytoskeleton;plasma membrane;focal adhesion;sarcoplasm;Z disc;sarcolemma;costamere
• Molecular function: protein binding;cytoskeletal protein binding;ankyrin binding;actin filament binding