TGM1 V518M - GET-Evidence


TGM1 V518M

(TGM1 Val518Met)

Short summary

Probably a non-pathogenic polymorphism. It was initially thought to be involved in autosomal recessive congenital ichthyosis, but later authors found the variant in numerous healthy controls.

Variant evidence
Computational -
Functional -
Case/Control 4

Allele frequency relatively common in controls

Familial 2

Does not segregate with disease

Clinical importance
Severity -
Treatability -
Penetrance -


Low clinical importance, Likely benign

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

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • T @ chr14:24724663: 1.1% (122/10756) in EVS
  • T @ chr14:23794502: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 1.1% (122/10756)


Herman ML, Farasat S, Steinbach PJ, Wei MH, Toure O, Fleckman P, Blake P, Bale SJ, Toro JR. Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1. Hum Mutat. 2009 Apr;30(4):537-47. Review. PubMed PMID: 19241467.

These authors examine various reports of the variant and conclude it is likely a non-pathogenic polymorphism, noting numerous findings in controls and lack of segregation in some affected families.


hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het T @ chr14:24724663


GS19669 - var-GS19669-1100-36-ASM
het T @ chr14:23794503


Other external references

  • rs35312232
  • GeneTests records for the TGM1 gene
    Autosomal Recessive Congenital Ichthyosis
    TGM1-Related Autosomal Recessive Congenital Ichthyosis
  • Score: 0.634 (possibly damaging)
    Web search results (9 hits -- see all)
  • Genotype/Phenotype Correlation in Autosomal Recessive ...
    tients not linked to the TGM1 gene, the second region. identiļ¬ed on ... Remarkably, mutation V518M re- sides much more distal in the TGM1 gene than any other ...
  • Journal of Investigative Dermatology - Transglutaminase 1 ...
    We have analyzed the TGM1 locus in six unrelated Italian families ... In the TGM1 gene of two LI families, we found three mis-sense mutations (V518M, E520G, and S272P) and the ...
  • Histochemie / Immunhistochemische Charakterisierung von ...
    Neue Punktmutationen auf TGM1 Gen wurden bei drei Patienten mit drastisch ... (V518M, E520G, S272P) und die bereits. bekannte "splice site" Mutation auf TGM1 Gen ...
  • Structural changes in epidermal scale and appendages as ...
    Structural changes in epidermal scale and appendages as indicators of defective TGM1 activity. - Robert H Rice, Debra Crumrine, Yoshikazu Uchida, Robert Gruber, Peter ...
  • Structural changes in epidermal scale and appendages as ...
    Defective transglutaminase 1 (TGM1) is a causative factor in some cases of lamellar ... the consequences of the V518M mutation in TGM1, about which conflicting reports have ...
  • Rice, RH (Robert H)
    A distal region of the human TGM1 promoter is required ... of TGM1 deficiency in vivo and (c) helps characterize the consequences of the V518M mutation in TGM1, about ...
  • OMIM: 190195
    MOLECULAR GENETICS Mutations in the TGM1 gene were found as the cause of autosomal ... met (V518M) mutation in the TGM1 gene. . 0019 ICHTHYOSIS, LAMELLAR, 1 TGM1, SER160CYS In ...
  • Transglutaminase 1 deficiency and corneocyte collapse: an ...
    BioInfoBank Library :: Transglutaminase 1 deficiency and corneocyte collapse: an indication for targeted molecular screening in autosomal recessive congenital ...

Other in silico analyses

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

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Gene search

"GENE" or "GENE A123C":

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