NM_001110556.2(FLNA):c.687G>A (p.Met229Ile) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 8, 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:: RCV002017038.6

Allele description [Variation Report for NM_001110556.2(FLNA):c.687G>A (p.Met229Ile)]

NM_001110556.2(FLNA):c.687G>A (p.Met229Ile)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.687G>A (p.Met229Ile)

HGVS:

NC_000023.11:g.154367674C>T
NG_011506.2:g.11965G>A
NM_001110556.2:c.687G>AMANE SELECT
NM_001456.4:c.687G>A
NP_001104026.1:p.Met229Ile
NP_001447.2:p.Met229Ile
LRG_1340t1:c.687G>A
LRG_1340:g.11965G>A
LRG_1340p1:p.Met229Ile
NC_000023.10:g.153596042C>T

Protein change:

M229I

Links:

dbSNP: rs886044820

NCBI 1000 Genomes Browser:

rs886044820

Molecular consequence:

NM_001110556.2:c.687G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001456.4:c.687G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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:: 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 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:: Frontometaphyseal dysplasia (FMD1)
Identifiers:: MONDO: MONDO:0015942; MedGen: C0265293; OMIM: PS305620

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002302157	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 8, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26404489, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002302157

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 8, 2021)

germline

clinical testing

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

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

Fetal phenotypes in otopalatodigital spectrum disorders.

Naudion S, Moutton S, Coupry I, Sole G, Deforges J, Guerineau E, Hubert C, Deves S, Pilliod J, Rooryck C, Abel C, Le Breton F, Collardeau-Frachon S, Cordier MP, Delezoide AL, Goldenberg A, Loget P, Melki J, Odent S, Patrier S, Verloes A, Viot G, et al.

Clin Genet. 2016 Mar;89(3):371-7. doi: 10.1111/cge.12679. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26404489

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, SCV002302157.3

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

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FLNA protein function. This variant has been observed in individual(s) with X-linked otopalatodigital spectrum disorders (PMID: 26404489). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 229 of the FLNA protein (p.Met229Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine.

#	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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