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NM_001458.5(FLNC):c.1848C>G (p.Ile616Met) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 3, 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:
RCV000524898.4

Allele description [Variation Report for NM_001458.5(FLNC):c.1848C>G (p.Ile616Met)]

NM_001458.5(FLNC):c.1848C>G (p.Ile616Met)

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.1848C>G (p.Ile616Met)
HGVS:
  • NC_000007.14:g.128841204C>G
  • NG_011807.1:g.15776C>G
  • NM_001127487.2:c.1848C>G
  • NM_001458.5:c.1848C>GMANE SELECT
  • NP_001120959.1:p.Ile616Met
  • NP_001449.3:p.Ile616Met
  • NP_001449.3:p.Ile616Met
  • LRG_870t1:c.1848C>G
  • LRG_870:g.15776C>G
  • LRG_870p1:p.Ile616Met
  • NC_000007.13:g.128481258C>G
  • NM_001458.4:c.1848C>G
Protein change:
I616M
Links:
dbSNP: rs770173704
NCBI 1000 Genomes Browser:
rs770173704
Molecular consequence:
  • NM_001127487.2:c.1848C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001458.5:c.1848C>G - 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
SCV000650922Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 3, 2021) 		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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000650922.4

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

Description

This sequence change replaces isoleucine with methionine at codon 616 of the FLNC protein (p.Ile616Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of FLNC-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 471989). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Jun 24, 2023