NM_001110556.2(FLNA):c.5972C>T (p.Ser1991Leu) AND multiple conditions

Germline classification:: Likely benign (2 submissions)
Last evaluated:: May 18, 2022
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:: RCV002498402.9

Allele description [Variation Report for NM_001110556.2(FLNA):c.5972C>T (p.Ser1991Leu)]

NM_001110556.2(FLNA):c.5972C>T (p.Ser1991Leu)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.5972C>T (p.Ser1991Leu)

Other names:

p.S1983L:TCG>TTG

HGVS:

NC_000023.11:g.154353346G>A
NG_011506.2:g.26293C>T
NM_001110556.2:c.5972C>TMANE SELECT
NM_001456.4:c.5948C>T
NP_001104026.1:p.Ser1991Leu
NP_001447.2:p.Ser1983Leu
LRG_1340t1:c.5972C>T
LRG_1340:g.26293C>T
LRG_1340p1:p.Ser1991Leu
NC_000023.10:g.153581714G>A
NM_001110556.1:c.5972C>T
NM_001456.3:c.5948C>T

Protein change:

S1991L

Links:

dbSNP: rs187029309

NCBI 1000 Genomes Browser:

rs187029309

Molecular consequence:

NM_001110556.2:c.5972C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001456.4:c.5948C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiac valvular dysplasia, X-linked (CVDPX)
Synonyms:: Valvular heart disease, congenital; Myxomatous valvular dystrophy, X-linked; Congenital valvular dysplasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010753; MedGen: C0262436; Orphanet: 1864; Orphanet: 75497; OMIM: 314400

Name:: FG syndrome 2 (FGS2)
Identifiers:: MONDO: MONDO:0010297; MedGen: C1845902; OMIM: 300321

Name:: Heterotopia, periventricular, X-linked dominant (PVNH1)
Synonyms:: PERIVENTRICULAR NODULAR HETEROTOPIA 1; X-linked periventricular heterotopia; Heterotopia familial nodular; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010233; MedGen: C1848213; Orphanet: 2149; Orphanet: 82004; OMIM: 300049

Name:: Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked (CIIPX)
Synonyms:: INTESTINAL PSEUDOOBSTRUCTION, NEURONAL, CHRONIC IDIOPATHIC, WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT; Congenital idiopathic intestinal pseudoobstruction; CIIP X-linked
Identifiers:: MONDO: MONDO:0010232; MedGen: C2746068; Orphanet: 2301; OMIM: 300048

Name:: Melnick-Needles syndrome (MNS)
Synonyms:: Melnick-Needles osteodysplasty; Osteodysplasty of Melnick and Needles
Identifiers:: MONDO: MONDO:0010650; MedGen: C0025237; Orphanet: 2484; OMIM: 309350

Name:: Oto-palato-digital syndrome, type I (OPD1)
Synonyms:: OPD I SYNDROME; Oto-palato-digital syndrome type 1; Taybi syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010704; MedGen: C0265251; Orphanet: 669; OMIM: 311300

Name:: Oto-palato-digital syndrome, type II (OPD2)
Synonyms:: OPD II SYNDROME; Oto-palato-digital syndrome type 2; Andre syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010571; MedGen: C1844696; Orphanet: 669; Orphanet: 90652; OMIM: 304120

Name:: Terminal osseous dysplasia-pigmentary defects syndrome
Synonyms:: ODPF SYNDROME; OSSEOUS DYSPLASIA, DIGITAL, WITH FACIAL PIGMENTARY DEFECTS AND MULTIPLE FRENULA; ODPD; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010279; MedGen: C1846129; Orphanet: 88630; OMIM: 300244

Name:: Frontometaphyseal dysplasia 1 (FMD1)
Identifiers:: MONDO: MONDO:0024550; MedGen: C4281559; Orphanet: 1826; OMIM: 305620

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002804403	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jan 7, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003919969	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (May 18, 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

SCV002804403

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jan 7, 2022)

unknown

clinical testing

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

SCV003919969

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(May 18, 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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV002804403.1

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

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

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003919969.1

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

Description

This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.3% (187/53291) including 1 homozygote and 43 hemizygotes (https://gnomad.broadinstitute.org/variant/X-154353346-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:93767). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine