NM_001458.5(FLNC):c.4946del (p.Gly1649fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 17, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001386350.7

Allele description [Variation Report for NM_001458.5(FLNC):c.4946del (p.Gly1649fs)]

NM_001458.5(FLNC):c.4946del (p.Gly1649fs)

Gene:

FLNC:filamin C [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_001458.5(FLNC):c.4946del (p.Gly1649fs)

HGVS:

NC_000007.14:g.128849199del
NG_011807.1:g.23771del
NM_001127487.2:c.4946del
NM_001458.5:c.4946delMANE SELECT
NP_001120959.1:p.Gly1649fs
NP_001449.3:p.Gly1649fs
LRG_870t1:c.4946del
LRG_870:g.23771del
NC_000007.13:g.128489252del
NC_000007.13:g.128489253del
NM_001458.4:c.4946delG

Protein change:

G1649fs

Links:

dbSNP: rs1282619643

NCBI 1000 Genomes Browser:

rs1282619643

Molecular consequence:

NM_001127487.2:c.4946del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001458.5:c.4946del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Myofibrillar myopathy 5
Synonyms:: FILAMINOPATHY, AUTOSOMAL DOMINANT; Myofibrillar myopathy, filamin C-related; Filaminopathy (type)
Identifiers:: MONDO: MONDO:0012289; MedGen: C1836050; OMIM: 609524

Name:: Distal myopathy with posterior leg and anterior hand involvement
Synonyms:: WILLIAMS DISTAL MYOPATHY; Myopathy, distal, 4
Identifiers:: MONDO: MONDO:0013550; MedGen: C3279722; Orphanet: 63273; OMIM: 614065

Name:: Hypertrophic cardiomyopathy 26
Synonyms:: Cardiomyopathy, familial hypertrophic, 26
Identifiers:: MONDO: MONDO:0014883; MedGen: C4310749; Orphanet: 75249; OMIM: 617047

Name:: Dilated Cardiomyopathy, Dominant
Identifiers:: MedGen: CN239310

Recent activity

Clear Turn Off Turn On

RecName: Full=Transcription factor DIVARICATA
RecName: Full=Transcription factor DIVARICATA
gi|75330977|sp|Q8S9H7.1|DIV_ANTMA

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001586541	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27908349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001586541

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 17, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies.

Ortiz-Genga MF, Cuenca S, Dal Ferro M, Zorio E, Salgado-Aranda R, Climent V, Padrón-Barthe L, Duro-Aguado I, Jiménez-Jáimez J, Hidalgo-Olivares VM, García-Campo E, Lanzillo C, Suárez-Mier MP, Yonath H, Marcos-Alonso S, Ochoa JP, Santomé JL, García-Giustiniani D, Rodríguez-Garrido JL, Domínguez F, Merlo M, Palomino J, et al.

J Am Coll Cardiol. 2016 Dec 6;68(22):2440-2451. doi: 10.1016/j.jacc.2016.09.927.

PubMed [citation]

PMID:: 27908349

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001586541.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1073366). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gly1649Alafs*17) in the FLNC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLNC are known to be pathogenic (PMID: 27908349).

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine