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NM_001458.5(FLNC):c.4471G>A (p.Val1491Met) AND Hypertrophic cardiomyopathy 26

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 6, 2021
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:
RCV002471020.1

Allele description [Variation Report for NM_001458.5(FLNC):c.4471G>A (p.Val1491Met)]

NM_001458.5(FLNC):c.4471G>A (p.Val1491Met)

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.4471G>A (p.Val1491Met)
HGVS:
  • NC_000007.14:g.128847959G>A
  • NG_011807.1:g.22531G>A
  • NM_001127487.2:c.4471G>A
  • NM_001458.5:c.4471G>AMANE SELECT
  • NP_001120959.1:p.Val1491Met
  • NP_001449.3:p.Val1491Met
  • NP_001449.3:p.Val1491Met
  • LRG_870t1:c.4471G>A
  • LRG_870:g.22531G>A
  • LRG_870p1:p.Val1491Met
  • NC_000007.13:g.128488013G>A
  • NM_001458.4:c.4471G>A
Protein change:
V1491M
Links:
dbSNP: rs186904046
NCBI 1000 Genomes Browser:
rs186904046
Molecular consequence:
  • NM_001127487.2:c.4471G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001458.5:c.4471G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767356Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 6, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Filamin C-related myopathies: pathology and mechanisms.

Fürst DO, Goldfarb LG, Kley RA, Vorgerd M, Olivé M, van der Ven PF.

Acta Neuropathol. 2013 Jan;125(1):33-46. doi: 10.1007/s00401-012-1054-9. Epub 2012 Oct 30.

PubMed [citation]
PMID:
23109048
PMCID:
PMC5127197

FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy.

Begay RL, Tharp CA, Martin A, Graw SL, Sinagra G, Miani D, Sweet ME, Slavov DB, Stafford N, Zeller MJ, Alnefaie R, Rowland TJ, Brun F, Jones KL, Gowan K, Mestroni L, Garrity DM, Taylor MR.

JACC Basic Transl Sci. 2016 Aug;1(5):344-359. doi: 10.1016/j.jacbts.2016.05.004. Epub 2016 Jul 27.

PubMed [citation]
PMID:
28008423
PMCID:
PMC5166708
See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767356.1

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with FLNC-related disease. Loss of function variants have been reported to cause myofibrillar myopathy, 5 (MIM#609524), distal myopathy, 4 (MIM#614065), familial hypertrophic cardiomyopathy, 26 (MIM#617047) and dilated cardiomyopathy. Gain of function variants have also been reported to cause distal myopathy, 4 (MIM#614065) (PMID: 28008423, PMID: 23109048). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from valine to methionine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (2 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated filamin-type immunoglobulin domain (NCBI conserved domain). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been reported as a VUS in ClinVar.(I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Sep 29, 2024