NM_001458.5(FLNC):c.6478A>T (p.Ile2160Phe) AND Cardiomyopathy, familial restrictive, 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 21, 2016
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000239590.1

Allele description [Variation Report for NM_001458.5(FLNC):c.6478A>T (p.Ile2160Phe)]

NM_001458.5(FLNC):c.6478A>T (p.Ile2160Phe)

Genes:

FLNC-AS1:FLNC antisense RNA 1 [Gene - HGNC]
FLNC:filamin C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_001458.5(FLNC):c.6478A>T (p.Ile2160Phe)

HGVS:

NC_000007.14:g.128853831A>T
NG_011807.1:g.28403A>T
NM_001127487.2:c.6379A>T
NM_001458.5:c.6478A>TMANE SELECT
NP_001120959.1:p.Ile2127Phe
NP_001449.3:p.Ile2160Phe
NP_001449.3:p.Ile2160Phe
LRG_870t1:c.6478A>T
LRG_870:g.28403A>T
LRG_870p1:p.Ile2160Phe
NC_000007.13:g.128493885A>T
NM_001458.4:c.6478A>T
Q14315:p.Ile2160Phe

Protein change:

I2127F; ILE2160PHE

Links:

UniProtKB: Q14315#VAR_077042; OMIM: 102565.0009; dbSNP: rs879255640

NCBI 1000 Genomes Browser:

rs879255640

Molecular consequence:

NM_001127487.2:c.6379A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001458.5:c.6478A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy, familial restrictive, 5 (RCM5)
Identifiers:: MONDO: MONDO:0800371; MedGen: C4310748

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000297925	OMIM	no assertion criteria provided	Pathogenic (Jul 21, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000297925

OMIM

no assertion criteria provided

Pathogenic
(Jul 21, 2016)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy.

Brodehl A, Ferrier RA, Hamilton SJ, Greenway SC, Brundler MA, Yu W, Gibson WT, McKinnon ML, McGillivray B, Alvarez N, Giuffre M, Schwartzentruber J; FORGE Canada Consortium., Gerull B.

Hum Mutat. 2016 Mar;37(3):269-79. doi: 10.1002/humu.22942. Epub 2016 Jan 8.

PubMed [citation]

PMID:: 26666891

Details of each submission

From OMIM, SCV000297925.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 4-generation Canadian family with restrictive cardiomyopathy (RCM5; see 617047), Brodehl et al. (2016) identified heterozygosity for a c.6478A-T transversion (c.6478A-T, NM_001458.4) in the FLNC gene, resulting in an ile2160-to-phe (I2160F) substitution at a highly conserved residue within the 19th immunoglobulin-like domain. The mutation segregated with disease and was not found in public variant databases, including the ExAC database. Immunohistochemical analysis of explanted cardiac tissue from the proband revealed that the normal intercalated disc localization of desmin (DES; 125660) was absent, but no obvious filamin-C aggregates were present. This family was evaluated after the asymptomatic 15-year-old female proband was diagnosed with severe diastolic dysfunction, enlarged atria, and elevated pulmonary pressure, suggesting RCM. Her brother, father, and paternal uncle were known to have cardiomyopathy, with features of RCM on echocardiography. In addition, 2 paternal first cousins had RCM.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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