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NM_001110556.2(FLNA):c.6146G>A (p.Arg2049His) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 29, 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:
RCV001361875.7

Allele description [Variation Report for NM_001110556.2(FLNA):c.6146G>A (p.Arg2049His)]

NM_001110556.2(FLNA):c.6146G>A (p.Arg2049His)

Gene:
FLNA:filamin A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001110556.2(FLNA):c.6146G>A (p.Arg2049His)
Other names:
p.Arg2041His
HGVS:
  • NC_000023.11:g.154353081C>T
  • NG_011506.2:g.26558G>A
  • NM_001110556.2:c.6146G>AMANE SELECT
  • NM_001456.4:c.6122G>A
  • NP_001104026.1:p.Arg2049His
  • NP_001447.2:p.Arg2041His
  • NP_001447.2:p.Arg2041His
  • LRG_1340t1:c.6146G>A
  • LRG_1340:g.26558G>A
  • LRG_1340p1:p.Arg2049His
  • NC_000023.10:g.153581449C>T
  • NM_001456.3:c.6122G>A
Protein change:
R2041H
Links:
dbSNP: rs1557176118
NCBI 1000 Genomes Browser:
rs1557176118
Molecular consequence:
  • NM_001110556.2:c.6146G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001456.4:c.6122G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001557866Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 29, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001557866.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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) performed at Invitae indicates that this missense variant is not expected to disrupt FLNA protein function. This variant has not been reported in the literature in individuals with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 492841). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 2041 of the FLNA protein (p.Arg2041His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024