NM_001110556.2(FLNA):c.6002G>A (p.Arg2001Gln) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 2, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000996065.26

Allele description [Variation Report for NM_001110556.2(FLNA):c.6002G>A (p.Arg2001Gln)]

NM_001110556.2(FLNA):c.6002G>A (p.Arg2001Gln)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.6002G>A (p.Arg2001Gln)

HGVS:

NC_000023.11:g.154353316C>T
NG_011506.2:g.26323G>A
NM_001110556.2:c.6002G>AMANE SELECT
NM_001456.4:c.5978G>A
NP_001104026.1:p.Arg2001Gln
NP_001447.2:p.Arg1993Gln
NP_001447.2:p.Arg1993Gln
LRG_1340t1:c.6002G>A
LRG_1340:g.26323G>A
LRG_1340p1:p.Arg2001Gln
NC_000023.10:g.153581684C>T
NM_001456.3:c.5978G>A

Protein change:

R1993Q

Links:

dbSNP: rs1483960506

NCBI 1000 Genomes Browser:

rs1483960506

Molecular consequence:

NM_001110556.2:c.6002G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001456.4:c.5978G>A - 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
SCV001150526	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jun 1, 2016)	germline	clinical testing	Citation Link,
SCV002569574	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 2, 2024)	germline	clinical testing	Citation Link,
SCV003800573	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (Mar 18, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001150526

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Jun 1, 2016)

germline

clinical testing

Citation Link,

SCV002569574

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 2, 2024)

germline

clinical testing

Citation Link,

SCV003800573

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Uncertain significance
(Mar 18, 2022)

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	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001150526.27

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV002569574.3

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified as hemizygous in a fetus with tetralogy of fallot and shown to be maternally inherited (reported as c.6002 G>A; p.(R2001Q)) (PMID: 32410215, 36307859); This variant is associated with the following publications: (PMID: 32410215, 36307859)

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003800573.2

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

Description

The FLNA c.5978G>A; p.Arg1993Gln variant (rs1483960506), also known as c.6002G>A; p.Arg2001Gln in transcript NM_001110556, is reported in the literature in a hemizygous fetus affected with tetralogy of Fallot (Li 2020). This variant is found on only three chromosomes (3/181587 alleles) in the Genome Aggregation Database. The arginine at codon 1993 is highly conserved, but computational analyses predict that this variant is neutral (REVEL: 0.131). Due to limited information, the clinical significance of the p.Arg1993Gln variant is uncertain at this time. References: Li R et al. Prenatal exome sequencing in fetuses with congenital heart defects. Clin Genet. 2020 Sep;98(3):215-230. PMID: 32410215.

#	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: Oct 20, 2024

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