NM_001110556.2(FLNA):c.586C>T (p.Arg196Trp) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Mar 26, 2024
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:: RCV000153245.18

Allele description [Variation Report for NM_001110556.2(FLNA):c.586C>T (p.Arg196Trp)]

NM_001110556.2(FLNA):c.586C>T (p.Arg196Trp)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.586C>T (p.Arg196Trp)

HGVS:

NC_000023.11:g.154367878G>A
NG_011506.2:g.11761C>T
NM_001110556.2:c.586C>TMANE SELECT
NM_001456.4:c.586C>T
NP_001104026.1:p.Arg196Trp
NP_001447.2:p.Arg196Trp
NP_001447.2:p.Arg196Trp
LRG_1340t1:c.586C>T
LRG_1340:g.11761C>T
LRG_1340p1:p.Arg196Trp
NC_000023.10:g.153596246G>A
NM_001110556.1:c.586C>T
NM_001456.3:c.586C>T
P21333:p.Arg196Trp

Protein change:

R196W; ARG196TRP

Links:

UniProtKB: P21333#VAR_015716; OMIM: 300017.0026; dbSNP: rs137853317

NCBI 1000 Genomes Browser:

rs137853317

Molecular consequence:

NM_001110556.2:c.586C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001456.4:c.586C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002820867	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 26, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002820867

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Mar 26, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans.

Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, Kenwrick SJ, Kim CA, Morava E, Newbury-Ecob R, Orstavik KH, Quarrell OW, Schwartz CE, Shears DJ, Suri M, Kendrick-Jones J, Wilkie AO; OPD-spectrum Disorders Clinical Collaborative Group..

Nat Genet. 2003 Apr;33(4):487-91. Epub 2003 Mar 3.

PubMed [citation]

PMID:: 12612583

A Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype-genotype correlation.

Kondoh T, Okamoto N, Norimatsu N, Uetani M, Nishimura G, Moriuchi H.

J Hum Genet. 2007;52(4):370-373. doi: 10.1007/s10038-007-0108-7. Epub 2007 Jan 31.

PubMed [citation]

PMID:: 17264970

Details of each submission

From Eurofins Ntd Llc (ga), SCV000202719.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

#	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		1	not provided	not provided	not provided

From GeneDx, SCV002820867.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33767182, 12612583, 17264970, 37010288)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000202719	Eurofins Ntd Llc (ga)	flagged submission Reason: Older and outlier claim with insufficient supporting evidence Notes: None (EGL Classification Definitions 2015)	Uncertain significance (Jan 21, 2014)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12612583, 17264970 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000202719

Eurofins Ntd Llc (ga)

flagged submission

Reason: Older and outlier claim with insufficient supporting evidence

Notes: None

(EGL Classification Definitions 2015)

Uncertain significance
(Jan 21, 2014)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Last Updated: Oct 26, 2024

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