MTTP D384A - GET-Evidence

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

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Curation:
Currentness:

MTTP D384A

(MTTP Asp384Ala)


Short summary

This variant was found in an individual with familial hypobetalipoproteinemia as part of a compound heterozygote with G661A and with a background of homozygosity for ApoE2.

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated benign

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

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr4:100521805: 7.9% (846/10758) in EVS
  • C @ chr4:100740827: 3.9% (5/128) in GET-Evidence
  • Frequency shown in summary reports: 7.9% (846/10758)

Publications
 

Rehberg EF, Samson-Bouma ME, Kienzle B, Blinderman L, Jamil H, Wetterau JR, Aggerbeck LP, Gordon DA. A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase. J Biol Chem. 1996 Nov 22;271(47):29945-52. PubMed PMID: 8939939.

 

Berthier MT, Couture P, Houde A, Paradis AM, Sammak A, Verner A, Deprés JP, Gagné C, Gaudet D, Vohl MC. The c.419-420insA in the MTP gene is associated with abetalipoproteinemia among French-Canadians. Mol Genet Metab. 2004 Feb;81(2):140-3. PubMed PMID: 14741197.

 

Di Leo E, Lancellotti S, Penacchioni JY, Cefalù AB, Averna M, Pisciotta L, Bertolini S, Calandra S, Gabelli C, Tarugi P. Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia. Atherosclerosis. 2005 Jun;180(2):311-8. Epub 2005 Jan 19. PubMed PMID: 15910857.

This variant was found in an individual with familial hypobetalipoproteinemia as part of a compound heterozygote with G661A and with a background of homozygosity for ApoE2. It was also seen in 4/100 controls. The authors cite Rehberg et al where the variant is found to have no in vitro effect, and Berthier et al. where it is found with a frequency of 18.3% in French-Canadians with seemingly no effect. They hypothesize that with a ApoE2 background a slight in vivo change may cause expression of the disease.

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het C @ chr4:100521805

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het C @ chr4:100521805

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het C @ chr4:100521805

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het C @ chr4:100521805

 

GS18505 - var-GS18505-1100-36-ASM
het C @ chr4:100740828

 

GS19701 - var-GS19701-1100-36-ASM
het C @ chr4:100740828

 

GS19703 - var-GS19703-1100-36-ASM
het C @ chr4:100740828

 

GS19834 - var-GS19834-1100-36-ASM
het C @ chr4:100740828

 

Other external references
 

    dbSNP
  • rs17029215
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.015 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 0

Edit history
 

Gene search

"GENE" or "GENE A123C":

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