TGIF1 P83Shift - GET-Evidence

Curation:
Currentness:

TGIF1 P83Shift

(TGIF1 83delPinsShift)


Short summary

Severe variants in this gene are associated with holoprosencephaly disorders when combined with loss-of-function variants in SHH. Haploinsufficiency was identified in some families with this condition. It is unclear how likely this variant is to occur in combination with an SHH variant, or what phenotypic effect the variant would have on its own.

Variant evidence
Computational 3

Variants in this gene are associated with the disorder, frameshift mutation

See Nanni L et al. 1999 (10556296).

Functional -
Case/Control

No case/control data

Familial -
 
Clinical importance
Severity 4

Can be severe craniofacial and brain defects

Treatability 1
Penetrance 1

In reported cases, occurs in combination with SHH mutations

See Nanni L et al. 1999 (10556296).

 

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

other

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr18:3442222: 13.9% (15/108) in GET-Evidence
  • Frequency shown in summary reports: 13.9% (15/108)

Publications
 

Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M. The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet. 1999 Dec;8(13):2479-88. PubMed PMID: 10556296.

SHH mutations are associated with holoprosencephaly, but TGIF variants have also been implicated as playing a role.

The authors analysis is that variants reducing TGIF function may exacerbate SHH variants by mimicking increased retinoic acid levels (by a reduction in TGIF’s normal competitive binding for the retinoic acid receptor). This could have the effect of decreasing SHH expression, thereby accentuating the effect of an SHH variant which already has reduced activity.

Genomes
 

 

hu04FD18

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het - @ chr18:3452223

 

 

 

 

 

 

 

 

 

 

hu43860C

 

 

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het - @ chr18:3452223

 

 

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
hom - @ chr18:3452223

 

 

 

GS06985 - var-GS06985-1100-36-ASM
het - @ chr18:3442223

 

GS07357 - var-GS07357-1100-36-ASM
het - @ chr18:3442223

 

GS10851 - var-GS10851-1100-36-ASM
het - @ chr18:3442223

 

GS18504 - var-GS18504-1100-36-ASM
het C @ chr18:3442223

 

GS18505 - var-GS18505-1100-36-ASM
het - @ chr18:3442223

 

GS18517 - var-GS18517-1100-36-ASM
het - @ chr18:3442223

 

GS18558 - var-GS18558-1100-36-ASM
het - @ chr18:3442223

 

GS19025 - var-GS19025-1100-36-ASM
het - @ chr18:3442223

 

GS19129 - var-GS19129-1100-36-ASM
het - @ chr18:3442223

 

GS19700 - var-GS19700-1100-36-ASM
het - @ chr18:3442223

 

GS19704 - var-GS19704-1100-36-ASM
het - @ chr18:3442223

 

GS19834 - var-GS19834-1100-36-ASM
het - @ chr18:3442223

 

Other external references
 

    dbSNP
  • rs11571510
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

  • NBLOSUM100 score = 4
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

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