NM_001458.5(FLNC):c.6907C>T (p.Gln2303Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV003097792.2

Allele description [Variation Report for NM_001458.5(FLNC):c.6907C>T (p.Gln2303Ter)]

NM_001458.5(FLNC):c.6907C>T (p.Gln2303Ter)

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.6907C>T (p.Gln2303Ter)

HGVS:

NC_000007.14:g.128854592C>T
NG_011807.1:g.29164C>T
NM_001127487.2:c.6808C>T
NM_001458.5:c.6907C>TMANE SELECT
NP_001120959.1:p.Gln2270Ter
NP_001449.3:p.Gln2303Ter
NP_001449.3:p.Gln2303Ter
LRG_870t1:c.6907C>T
LRG_870:g.29164C>T
LRG_870p1:p.Gln2303Ter
NC_000007.13:g.128494646C>T
NM_001458.4:c.6907C>T

Protein change:

Q2270*

Molecular consequence:

NM_001127487.2:c.6808C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001458.5:c.6907C>T - 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
SCV002959574	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32112656, 27908349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002959574

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 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 mutation update for the FLNC gene in myopathies and cardiomyopathies.

Verdonschot JAJ, Vanhoutte EK, Claes GRF, Helderman-van den Enden ATJM, Hoeijmakers JGJ, Hellebrekers DMEI, de Haan A, Christiaans I, Lekanne Deprez RH, Boen HM, van Craenenbroeck EM, Loeys BL, Hoedemaekers YM, Marcelis C, Kempers M, Brusse E, van Waning JI, Baas AF, Dooijes D, Asselbergs FW, Barge-Schaapveld DQCM, Koopman P, et al.

Hum Mutat. 2020 Jun;41(6):1091-1111. doi: 10.1002/humu.24004. Epub 2020 Mar 20. Review.

PubMed [citation]

PMID:: 32112656
PMCID:: PMC7318287

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 Invitae, SCV002959574.2

#	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. This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 32112656). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln2303*) 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: Apr 6, 2024

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