NM_001458.5(FLNC):c.7328G>A (p.Arg2443Gln) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 3, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000544906.3

Allele description [Variation Report for NM_001458.5(FLNC):c.7328G>A (p.Arg2443Gln)]

NM_001458.5(FLNC):c.7328G>A (p.Arg2443Gln)

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.7328G>A (p.Arg2443Gln)
HGVS:
  • NC_000007.14:g.128856594G>A
  • NG_011807.1:g.31166G>A
  • NM_001127487.2:c.7229G>A
  • NM_001458.4:c.7328G>A
  • NM_001458.5:c.7328G>AMANE SELECT
  • NP_001120959.1:p.Arg2410Gln
  • NP_001449.3:p.Arg2443Gln
  • NP_001449.3:p.Arg2443Gln
  • LRG_870t1:c.7328G>A
  • LRG_870:g.31166G>A
  • LRG_870p1:p.Arg2443Gln
  • NC_000007.13:g.128496648G>A
Protein change:
R2410Q
Links:
dbSNP: rs370293647
NCBI 1000 Genomes Browser:
rs370293647
Molecular consequence:
  • NM_001127487.2:c.7229G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001458.4:c.7328G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001458.5:c.7328G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Myofibrillar myopathy, filamin C-related (MFM5)
Synonyms:
FILAMINOPATHY, AUTOSOMAL DOMINANT; MYOPATHY, MYOFIBRILLAR, 5; Filaminopathy (type)
Identifiers:
MONDO: MONDO:0012289; MedGen: C1836050; OMIM: 609524
Name:
Myopathy, distal, 4 (MPD4)
Synonyms:
WILLIAMS DISTAL MYOPATHY
Identifiers:
MONDO: MONDO:0013550; MedGen: C3279722; Orphanet: 63273; OMIM: 614065
Name:
Cardiomyopathy, familial hypertrophic, 26 (CMH26)
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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000651161Invitaecriteria provided, single submitter
Uncertain significance
(Jul 3, 2018)
germlineclinical testing

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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000651161.3

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

Description

This sequence change replaces arginine with glutamine at codon 2443 of the FLNC protein (p.Arg2443Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs370293647, ExAC 0.01%) but has not been reported in the literature in individuals with a FLNC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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: Oct 25, 2021

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