NM_001110556.2(FLNA):c.695C>G (p.Ala232Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 23, 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:: RCV003802804.2

Allele description [Variation Report for NM_001110556.2(FLNA):c.695C>G (p.Ala232Gly)]

NM_001110556.2(FLNA):c.695C>G (p.Ala232Gly)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.695C>G (p.Ala232Gly)

HGVS:

NC_000023.11:g.154367666G>C
NG_011506.2:g.11973C>G
NM_001110556.2:c.695C>GMANE SELECT
NM_001456.4:c.695C>G
NP_001104026.1:p.Ala232Gly
NP_001447.2:p.Ala232Gly
LRG_1340t1:c.695C>G
LRG_1340:g.11973C>G
LRG_1340p1:p.Ala232Gly
NC_000023.10:g.153596034G>C

Protein change:

A232G

Molecular consequence:

NM_001110556.2:c.695C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001456.4:c.695C>G - 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
SCV004591786	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 23, 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

SCV004591786

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 23, 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, SCV004591786.1

#	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNA protein function. This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 232 of the FLNA protein (p.Ala232Gly).

#	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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