NM_001458.5(FLNC):c.5996G>A (p.Arg1999Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 17, 2023
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:: RCV000560676.8

Allele description [Variation Report for NM_001458.5(FLNC):c.5996G>A (p.Arg1999Gln)]

NM_001458.5(FLNC):c.5996G>A (p.Arg1999Gln)

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.5996G>A (p.Arg1999Gln)

HGVS:

NC_000007.14:g.128852744G>A
NG_011807.1:g.27316G>A
NM_001127487.2:c.5897G>A
NM_001458.5:c.5996G>AMANE SELECT
NP_001120959.1:p.Arg1966Gln
NP_001449.3:p.Arg1999Gln
NP_001449.3:p.Arg1999Gln
LRG_870t1:c.5996G>A
LRG_870:g.27316G>A
LRG_870p1:p.Arg1999Gln
NC_000007.13:g.128492798G>A
NM_001458.4:c.5996G>A

Protein change:

R1966Q

Links:

dbSNP: rs1346364708

NCBI 1000 Genomes Browser:

rs1346364708

Molecular consequence:

NM_001127487.2:c.5897G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001458.5:c.5996G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000651099	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27574918, 30418145, 32528171, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000651099

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 17, 2023)

germline

clinical testing

PubMed (4)
[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

Spectrum of Mutations in Hypertrophic Cardiomyopathy Genes Among Tunisian Patients.

Jaafar N, Gómez J, Kammoun I, Zairi I, Amara WB, Kachboura S, Kraiem S, Hammami M, Iglesias S, Alonso B, Coto E.

Genet Test Mol Biomarkers. 2016 Nov;20(11):674-679. Epub 2016 Aug 30.

PubMed [citation]

PMID:: 27574918

[Genotype-phenotype correlations of pathogenic variants in the FLNC gene].

Ader F, Villard E, Ledeuil C, Charron P, Richard P.

Med Sci (Paris). 2018 Nov;34 Hors série n°2:39-41. doi: 10.1051/medsci/201834s211. Epub 2018 Nov 12. French. No abstract available.

PubMed [citation]

PMID:: 30418145

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000651099.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1999 of the FLNC protein (p.Arg1999Gln). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individuals with hypertrophic cardiomyopathy and/or muscle weakness (PMID: 27574918, 30418145, 32528171; Invitae). ClinVar contains an entry for this variant (Variation ID: 472119). 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.

#	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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