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NM_001458.5(FLNC):c.5071G>A (p.Asp1691Asn) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 25, 2024
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:
RCV000691625.14

Allele description [Variation Report for NM_001458.5(FLNC):c.5071G>A (p.Asp1691Asn)]

NM_001458.5(FLNC):c.5071G>A (p.Asp1691Asn)

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.5071G>A (p.Asp1691Asn)
HGVS:
  • NC_000007.14:g.128849450G>A
  • NG_011807.1:g.24022G>A
  • NM_001127487.2:c.5071G>A
  • NM_001458.5:c.5071G>AMANE SELECT
  • NP_001120959.1:p.Asp1691Asn
  • NP_001449.3:p.Asp1691Asn
  • NP_001449.3:p.Asp1691Asn
  • LRG_870t1:c.5071G>A
  • LRG_870:g.24022G>A
  • LRG_870p1:p.Asp1691Asn
  • NC_000007.13:g.128489504G>A
  • NM_001458.4:c.5071G>A
Protein change:
D1691N
Links:
dbSNP: rs777061037
NCBI 1000 Genomes Browser:
rs777061037
Molecular consequence:
  • NM_001127487.2:c.5071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001458.5:c.5071G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000819411Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 25, 2024) 		germlineclinical testing

PubMed (4)
[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

Clinical, Pathological, and Genetic Features of Two Chinese Cases with Filamin C Myopathy.

Zhang YT, Pu CQ, Ban R, Liu HX, Shi Q, Lu XH.

Chin Med J (Engl). 2018 Dec 20;131(24):2986-2988. doi: 10.4103/0366-6999.247208. No abstract available.

PubMed [citation]
PMID:
30539912
PMCID:
PMC6302653

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]
PMID:
30847666
PMCID:
PMC6533346
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819411.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1691 of the FLNC protein (p.Asp1691Asn). This variant is present in population databases (rs777061037, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with hypertrophic cardiomyopathy, left ventricular non-compaction, and/or myofibrillar myopathy (PMID: 30539912, 30847666, 33890751). ClinVar contains an entry for this variant (Variation ID: 570701). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 24, 2024