FLNA A1764T - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

FLNA A1764T

(FLNA Ala1764Thr)


Short summary

Associated with periventricular nodular heterotopia in a sporadic female case.

Variant evidence
Computational 1

Gene associated with this disease.

See Sheen VL et al. 2001 (11532987).

Functional -
Case/Control

Not enough information to establish this.

Familial

Sporadic case reported.

 
Clinical importance
Severity 4
Treatability 1
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Total cases/controls case+ case– control+ control– p-value odds ratio
Periventricular Heterotopia, X-Linked
1 60 0 0 - -

 

Allele frequency

  • T @ chrX:153583007: 4.3% (341/7910) in EVS
  • T @ chrX:153236200: 5.6% (5/90) in GET-Evidence
  • Frequency shown in summary reports: 4.3% (341/7910)

Publications
 

Sheen VL, Dixon PH, Fox JW, Hong SE, Kinton L, Sisodiya SM, Duncan JS, Dubeau F, Scheffer IE, Schachter SC, Wilner A, Henchy R, Crino P, Kamuro K, DiMario F, Berg M, Kuzniecky R, Cole AJ, Bromfield E, Biber M, Schomer D, Wheless J, Silver K, Mochida GH, Berkovic SF, Andermann F, Andermann E, Dobyns WB, Wood NW, Walsh CA. Mutations in the X-linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females. Hum Mol Genet. 2001 Aug 15;10(17):1775-83. PubMed PMID: 11532987.

In a screen for variants in FLNA1 in 6 pedigrees and 55 individuals with periventricular nodular heterotopia, this variant was found in one sporadic female patient. She has 5 sons (and no daughters — this is contrast to the typical excess of daughters due to lethality of the variant in males) — two are mentally retarded, but it cannot be confirmed if they carry this variant or if this is the cause. No controls are reported.

Cases/controls case+ case– control+ control– p-value odds ratio
Periventricular Heterotopia, X-Linked
1 60 - - - -

 

Genomes
 

GS18504 - var-GS18504-1100-36-ASM
hom T @ chrX:153236201

 

GS18505 - var-GS18505-1100-36-ASM
het T @ chrX:153236201

 

GS18508 - var-GS18508-1100-36-ASM
het T @ chrX:153236201

 

GS19238 - var-GS19238-1100-36-ASM
het T @ chrX:153236201

 

GS19703 - var-GS19703-1100-36-ASM
hom T @ chrX:153236201

 

NA19240

 

show discussion

Discussion

This area of NA19240’s genome has been re-sequenced and the variant has been re-confirmed to be a heterozygous T.

Other external references
 

    dbSNP
  • rs57108893
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the FLNA gene
    FLNA-Related Disorders
    Otopalatodigital Spectrum Disorders
    Otopalatodigital Syndrome, Type I
    Otopalatodigital Syndrome, Type II
    Periventricular Heterotopia, X-Linked
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FLNA
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (2 hits -- see all)
  • letter
    FLNA, is a widely expressed protein that regulates re-organiza ... Fig. 1 Phenotype of the OPD-spectrum disorders caused by mutations in FLNA. ...
    www.isds.ch/PDF Files/Robertson Filamin A spectrum.pdf
  • Mutations in the X-linked filamin 1 gene cause ...
    ... LeuPhe substitution at amino acid 656; A1764T, AlaThr substitution at amino acid 1764) ... Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac ...
    hmg.oxfordjournals.org/cgi/content/full/10/17/1775

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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