MUSK T100M - GET-Evidence

Curation:
Currentness:

MUSK T100M

(MUSK Thr100Met)


Short summary

Probably benign.

Variant evidence
Computational

Polyphen 2 has intermediate result “possibly damaging”

Functional -
Case/Control 4

Allele frequency of ~1% inconsistent with rarity of severe pathogenic effect of Congenital Myasthenic Syndrome caused by severe MUSK mutations

See unpublished research (below).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

Disseration by Sofia Petrova, “Analyse des MUSK- und des COLQ-Gens bei Patienten mit kongenitalem myasthenen Syndrom” 2007 for Medizinischen Fakultät derLudwig-Maximilians-Universität zu München. Using Google Translate, it looks like this dissertation lists T100M as a nonpathogenic polymorphism seen in one patient & father.

CMS is quite rare, GeneReviews seems to support ~ 1 / 100,000 as a high end estimate. An as-yet-undiscovered pathogenic responsible for 10% of disease might be expected to have an allele frequency of .03% (.1 * (1 / 100,000)**0.5). The chances of seeing such a rare variant in twice in 124 random alleles is quite low (p=0.0007).

Allele frequency

  • T @ chr9:113449489: 2.3% (239/10208) in EVS
  • T @ chr9:112489309: 1.6% (2/124) in GET-Evidence
  • Frequency shown in summary reports: 2.3% (239/10208)

Publications
 

Genomes
 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het T @ chr9:113449489

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr9:113449489

 

GS06994 - var-GS06994-1100-36-ASM
het T @ chr9:112489310

 

Other external references
 

    dbSNP
  • rs35142681
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.488 (possibly damaging)
    Web search results (2 hits -- see all)
  • Analyse des MUSK- und des COLQ-Gens bei Patienten mit ...
    MuSK ist eine muskelspezifische Rezeptor-Tyrosinkinase, die eine wichtige Rolle ... festgestellt: T100M, bei dem der Ersatz von Cytosin durch Thymin zum Austausch ...
    edoc.ub.uni-muenchen.de/7858/1/Petrova_Sofia.pdf
  • Le blog de jyhzzp
    jyhzzp hébergé par over-blog.com ... masterbate buy buy gemstones cheap musk oil immanuels church in silver spring maryl cheap flights shannon to detroit fnb credit ...
    jyhzzp.over-blog.com

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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