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NM_001458.5(FLNC):c.6129G>T (p.Lys2043Asn) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 17, 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:
RCV003783452.1

Allele description [Variation Report for NM_001458.5(FLNC):c.6129G>T (p.Lys2043Asn)]

NM_001458.5(FLNC):c.6129G>T (p.Lys2043Asn)

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.6129G>T (p.Lys2043Asn)
HGVS:
  • NC_000007.14:g.128852952G>T
  • NG_011807.1:g.27524G>T
  • NM_001127487.2:c.6030G>T
  • NM_001458.5:c.6129G>TMANE SELECT
  • NP_001120959.1:p.Lys2010Asn
  • NP_001449.3:p.Lys2043Asn
  • NP_001449.3:p.Lys2043Asn
  • LRG_870t1:c.6129G>T
  • LRG_870:g.27524G>T
  • LRG_870p1:p.Lys2043Asn
  • NC_000007.13:g.128493006G>T
  • NM_001458.4:c.6129G>T
Protein change:
K2010N
Molecular consequence:
  • NM_001127487.2:c.6030G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001458.5:c.6129G>T - 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
SCV004568764Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 17, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV004568764.1

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

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. 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. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs775167656, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2043 of the FLNC protein (p.Lys2043Asn).

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

Last Updated: Mar 5, 2024