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NM_001458.5(FLNC):c.1676+1G>A AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 22, 2017
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:
RCV001379592.5

Allele description [Variation Report for NM_001458.5(FLNC):c.1676+1G>A]

NM_001458.5(FLNC):c.1676+1G>A

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.1676+1G>A
HGVS:
  • NC_000007.14:g.128840675G>A
  • NG_011807.1:g.15247G>A
  • NM_001127487.2:c.1676+1G>A
  • NM_001458.5:c.1676+1G>AMANE SELECT
  • LRG_870t1:c.1676+1G>A
  • LRG_870:g.15247G>A
  • NC_000007.13:g.128480729G>A
  • NM_001458.4:c.1676+1G>A
Links:
dbSNP: rs111452612
NCBI 1000 Genomes Browser:
rs111452612
Molecular consequence:
  • NM_001127487.2:c.1676+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001458.5:c.1676+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001577418Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 22, 2017) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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, SCV001577418.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant has not been reported in the literature in individuals with FLNC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 10 of the FLNC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FLNC are known to be pathogenic (PMID: 27908349).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024