NM_001458.5(FLNC):c.1948C>G (p.Arg650Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 26, 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:: RCV000685417.7

Allele description [Variation Report for NM_001458.5(FLNC):c.1948C>G (p.Arg650Gly)]

NM_001458.5(FLNC):c.1948C>G (p.Arg650Gly)

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.1948C>G (p.Arg650Gly)

HGVS:

NC_000007.14:g.128841304C>G
NG_011807.1:g.15876C>G
NM_001127487.2:c.1948C>G
NM_001458.5:c.1948C>GMANE SELECT
NP_001120959.1:p.Arg650Gly
NP_001449.3:p.Arg650Gly
NP_001449.3:p.Arg650Gly
LRG_870t1:c.1948C>G
LRG_870:g.15876C>G
LRG_870p1:p.Arg650Gly
NC_000007.13:g.128481358C>G
NM_001458.4:c.1948C>G

Protein change:

R650G

Links:

dbSNP: rs770606675

NCBI 1000 Genomes Browser:

rs770606675

Molecular consequence:

NM_001127487.2:c.1948C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001458.5:c.1948C>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

Recent activity

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RecName: Full=NEDD4 family-interacting protein 2; AltName: Full=NEDD4 WW domain-...
RecName: Full=NEDD4 family-interacting protein 2; AltName: Full=NEDD4 WW domain-binding protein 5A; AltName: Full=Putative MAPK-activating protein PM04/PM05/PM06/PM07; AltName: Full=Putative NF-kappa-B-activating protein 413
gi|73921209|sp|Q9NV92.2|NFIP2_HUMAN

Protein
Homologene neighbors for GEO Profiles (Select 59313728) (0)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 122900121) (20)
GEO Profiles
BioProjects for Gene (Select 100506457) (3)
BioProject
KCND1 potassium voltage-gated channel subfamily D member 1 [Homo sapiens]
KCND1 potassium voltage-gated channel subfamily D member 1 [Homo sapiens]
Gene ID:3750

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000812896	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000812896

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 26, 2022)

germline

clinical testing

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

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000812896.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 565776). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs770606675, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 650 of the FLNC protein (p.Arg650Gly).

#	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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