TSC1 T899S - GET-Evidence

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Curation:
Currentness:

TSC1 T899S

(TSC1 Thr899Ser)


Short summary

This variant was found in one sporadic case of Tuberous Sclerosis in a Japanese individual. Missense mutations are rarely causative for this disease, however.

Variant evidence
Computational 1

Gene associated with disease, but NBLOSUM=-1, missense mutations are rarely causative

See Zhang H et al. 1999 (10570911), Yamamoto T et al. 2002 (12015165), unpublished research (below).

Functional -
Case/Control 1

OR = 5.56, p = 0.07

Familial -
 
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

Yamamoto et al. claim that the variant is not causative due to the rarity of causative missense mutations in TSC1.

Total cases/controls case+ case– control+ control– p-value odds ratio
Tuberous Sclerosis 1
2 45 0 124 0.0744

 

Allele frequency

  • C @ chr9:134762747: 0.8% (1/126) in GET-Evidence
  • Frequency shown in summary reports: 0.8% (1/126)

Publications
 

Zhang H, Nanba E, Yamamoto T, Ninomiya H, Ohno K, Mizuguchi M, Takeshita K. Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex. J Hum Genet. 1999;44(6):391-6. Erratum in: J Hum Genet 2000;45(4):269. PubMed PMID: 10570911.

In a screen for mutations in TSC1 and TSC2 in 38 Japanese individuals with Tuberous Sclerosis, this variant was found sporadically in a 32yo female with angiofibroma, white macules, subependymal nodules and seizures. It was not seen in 60 controls.

Cases/controls case+ case– control+ control– p-value odds ratio
Tuberous Sclerosis 1
1 37 0 60 0.3878

 

Yamamoto T, Pipo JR, Feng JH, Takeda H, Nanba E, Ninomiya H, Ohno K. Novel TSC1 and TSC2 mutations in Japanese patients with tuberous sclerosis complex. Brain Dev. 2002 Jun;24(4):227-30. PubMed PMID: 12015165.

In a screen for TSC1 and TSC2 mutations in 9 Japanese individuals with tuberous sclerosis, this variant was seen as a compound heterozygote (with TSC2 L345R)) in a 6yo female with neurological symptoms, dermatological lesions and brain radiological findings. The variant was not seen in 64 Japanese and 55 Caucasian controls. This variant is reported as not causative due to the dearth of missense mutations in TSC1 causing tuberous sclerosis.

Cases/controls case+ case– control+ control– p-value odds ratio
Tuberous Sclerosis 1
1 8 0 64 0.1233

 

Genomes
 

GS18956 - var-GS18956-1100-36-ASM
het C @ chr9:134762748

 

Other external references
 

    PolyPhen-2
  • Score: 0 (benign)

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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