MEFV P369S - GET-Evidence

Curation:
Currentness:

MEFV P369S

(MEFV Pro369Ser)


Short summary

Weak evidence associating this with familial mediterranean fever, but there is a fairly high frequency of this allele. This variant might cause increased susceptibility to the disease but there is not enough evidence to be significant.

Variant evidence
Computational 1

Other mutations in this disease are associated with the disease.

See Aksentijevich I et al. 1999 (10090880), unpublished research (below).

Functional -
Case/Control

Not statistically significant

See Aksentijevich I et al. 1999 (10090880).

Familial

See unpublished research (below).

 
Clinical importance
Severity 3
Treatability 4

Colchicine treatment alleviates symptoms

Penetrance 2

May cause increased susceptibility

See Aksentijevich I et al. 1999 (10090880), Sugiura T et al. 2008 (18097735).

 

Impact

Low clinical importance, Uncertain pathogenic

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

In Counsyl diagnostic screen
http://precedings.nature.com/documents/4192/version/1

Total cases/controls case+ case– control+ control– p-value odds ratio
Familial Mediterranean Fever
5 177 59 1187 0.3348 0.568

 

Allele frequency

  • A @ chr16:3299586: 0.5% (55/10758) in EVS
  • A @ chr16:3239586: 2.3% (3/128) in GET-Evidence
  • Frequency shown in summary reports: 0.5% (55/10758)

Publications
 

Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, Wood G, Azzaro MP, Palumbo G, Giustolisi R, Pras M, Ostrer H, Kastner DL. Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet. 1999 Apr;64(4):949-62. PubMed PMID: 10090880; PubMed Central PMCID: PMC1377819.

In a screen for mutations in MEFV in patients with familial mediterranean fever, 4 out of 180 patient chromosomes had this variant. Only 1 out of 222 control chromosomes had it.

Cases/controls case+ case– control+ control– p-value odds ratio
Familial Mediterranean Fever
4 176 1 221 0.1778 5.023

 

Sugiura T, Kawaguchi Y, Fujikawa S, Hirano Y, Igarashi T, Kawamoto M, Takagi K, Hara M, Kamatani N. Familial Mediterranean fever in three Japanese patients, and a comparison of the frequency of MEFV gene mutations in Japanese and Mediterranean populations. Mod Rheumatol. 2008;18(1):57-9. Epub 2007 Dec 22. PubMed PMID: 18097735.

This variant was seen as part of a compound het (with R408Q) in a 17yo Japanese male with probable FMF (first episode at 6yo). His mother had the same genotype and was asymptomatic. In an analysis of 512 Japanese individuals (1024 chromosomes), the allelic frequency was determined to 0.057. Two control individuals were homozygous for both variants, and LD with R408Q is 1. The authors conclude that they may be weakly involved in the development of FMF.

Cases/controls case+ case– control+ control– p-value odds ratio
Familial Mediterranean Fever
1 1 58 966 0.1118 16.655

 

Genomes
 

 

GS18504 - var-GS18504-1100-36-ASM
het A @ chr16:3239587

 

GS18526 - var-GS18526-1100-36-ASM
het A @ chr16:3239587

 

GS18947 - var-GS18947-1100-36-ASM
het A @ chr16:3239587

 

Other external references
 

    dbSNP
  • rs11466023
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.995 (probably damaging)
    Web search results (266 hits -- see all)
  • Molecular Study of FMF Patients in Armenia
    Molecular analysis of MEFV gene mutations in 3000 Armenian patients ... phenotype, as well P369S, which was found in asymptomatic carriers. Based on these data ...
    www.bentham.org/cdtia/sample/cdtia4-1/0018L.pdf
  • Mutation and Haplotype Studies of Familial Mediterranean ...
    presence of three frequent MEFV mutations in multiple. Mediterranean populations strongly ... endonuclease analyses of PCR products were used for E148Q, P369S, and ...
    sciencedirect.com/science?_ob=MImg&...&ie=/sdarticle.pdf
  • FMF 2005
    Study of MEFV Mutations in the Iranian Population by Means of Reverse-Hybridization Teststrips ... 9.6% of MEFV genes. Five other mutations (P369S, M694V, V726A, A744S, ...
    niams.nih.gov/News_and_Events/Meetings_and_Events/...?ID=157
  • Molecular analysis of MEFV gene mutations among Palestinian ...
    RESULTS: We found that 40.5% of the samples had nine different MEFV mutations and one polymorphism. ... The mutations A744S, P369S, R408Q, and F479L were reported for the ...
    www.ncbi.nlm.nih.gov/pubmed/18609258
  • MEFV-Gene Analysis in Armenian Patients with Familial ...
    MEFV-Gene Analysis in Armenian Patients with Familial Mediterranean ... E148Q-P369S-R408Q. b. 1 (.6) Unidentified allele. 12 (7.4) Total. 163 (100) B. MEFV Gene ...
    sciencedirect.com/science?_ob=MImg&...&ie=/sdarticle.pdf
  • IMBB>Research Groups>Research
    Frequency of MEFV gene mutations both in FMF patients as well as in healthy controls from ... focused on 12 MEFV mutations (E148Q, P369S, F479L, M680I (G/C), M680I ...
    www.imbb.forth.gr/people/boumpas/group_IV.html
  • FMF
    of cases, other MEFV mutations are rare, and the various com ... The assay covers the following 12 MEFV mutations: E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, ...
    www.pentagen.cz/data/document/FMF.pdf
  • 日本人RA患者におけるMEFV変異
    Allele frequency of R408Q, P369S, E148Q, L110P mutations account respectively for 3.3 ... However, our data suggest that the MEFV gene mutations may not be a genetic factor ...
    docguide.com/news/content.nsf/dgcustomnews/...&lan=English
  • 1948
    the simultaneous detection of 12 MEFV mutations: E148Q. in exon 2, P369S in exon 3, F479L in exon 5, and M680I ... of any of the 12 MEFV mutations as well as. correctly identify ...
    www.clinchem.org/cgi/reprint/49/11/1948.pdf
  • MEFV
    genomic sequence of the MEFV gene were scanned by direct sequencing. ... Our data provide evidence that rare missense variants of the MEFV gene are, collectively, ...
    www.fibromyalgiatreatment.com/FMS-PlosOne.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 6

Edit history
 

Gene search

"GENE" or "GENE A123C":

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