NM_001458.5(FLNC):c.102G>A (p.Trp34Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 26, 2022
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:: RCV001932047.4

Allele description [Variation Report for NM_001458.5(FLNC):c.102G>A (p.Trp34Ter)]

NM_001458.5(FLNC):c.102G>A (p.Trp34Ter)

Gene:

FLNC:filamin C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_001458.5(FLNC):c.102G>A (p.Trp34Ter)

HGVS:

NC_000007.14:g.128830739G>A
NG_011807.1:g.5311G>A
NM_001127487.2:c.102G>A
NM_001458.5:c.102G>AMANE SELECT
NP_001120959.1:p.Trp34Ter
NP_001449.3:p.Trp34Ter
LRG_870:g.5311G>A
NC_000007.13:g.128470793G>A

Protein change:

W34*

Links:

dbSNP: rs2128932126

NCBI 1000 Genomes Browser:

rs2128932126

Molecular consequence:

NM_001127487.2:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001458.5:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002117502	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 26, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30935706, 27908349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002117502

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 26, 2022)

germline

clinical testing

PubMed (3)
[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

A Novel Truncating Variant in FLNC-Encoded Filamin C May Serve as a Proarrhythmic Genetic Substrate for Arrhythmogenic Bileaflet Mitral Valve Prolapse Syndrome.

Bains S, Tester DJ, Asirvatham SJ, Noseworthy PA, Ackerman MJ, Giudicessi JR.

Mayo Clin Proc. 2019 May;94(5):906-913. doi: 10.1016/j.mayocp.2018.11.028. Epub 2019 Mar 29.

PubMed [citation]

PMID:: 30935706

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002117502.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1361957). This premature translational stop signal has been observed in individual(s) with clinical features of FLNC-related conditions (PMID: 30935706). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp34*) 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

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