TYR P406L - GET-Evidence

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

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Curation:
Currentness:

TYR P406L

(TYR Pro406Leu)


Short summary

Reported to cause albinism in a recessive manner

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

Impact

Insufficiently evaluated pathogenic

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr11:89017973: 0.4% (39/10758) in EVS
  • Frequency shown in summary reports: 0.4% (39/10758)

Publications
 

Giebel LB, Tripathi RK, Strunk KM, Hanifin JM, Jackson CE, King RA, Spritz RA. Tyrosinase gene mutations associated with type IB ("yellow") oculocutaneous albinism. Am J Hum Genet. 1991 Jun;48(6):1159-67. Erratum in: Am J Hum Genet 1991 Sep;49(3):696. PubMed PMID: 1903591; PubMed Central PMCID: PMC1683101.

 

Toyofuku K, Wada I, Spritz RA, Hearing VJ. The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. Biochem J. 2001 Apr 15;355(Pt 2):259-69. PubMed PMID: 11284711; PubMed Central PMCID: PMC1221735.

 

King RA, Pietsch J, Fryer JP, Savage S, Brott MJ, Russell-Eggitt I, Summers CG, Oetting WS. Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. Hum Genet. 2003 Nov;113(6):502-13. Epub 2003 Sep 10. PubMed PMID: 13680365.

 

Hutton SM, Spritz RA. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. J Invest Dermatol. 2008 Oct;128(10):2442-50. Epub 2008 May 8. PubMed PMID: 18463683.

 

Council ML, Gardner JM, Helms C, Liu Y, Cornelius LA, Bowcock AM. Contribution of genetic factors for melanoma susceptibility in sporadic US melanoma patients. Exp Dermatol. 2009 May;18(5):485-7. Epub 2009 Mar 6. PubMed PMID: 19320745.

 

Genomes
 

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het T @ chr11:89017973

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het T @ chr11:89017973

 

Other external references
 

    dbSNP
  • rs104894313
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.996 (probably damaging)
    Web search results (15 hits -- see all)
  • Retina International's Scientific Newsletter - Tyrosinase ...
    OCA1A. Cys 55 Tyr. TGT-TAT. 0165. 1. Disrupts disulfide bond or elminates ... Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous ...
    www.retina-international.com/sci-news/tyrmut.htm
  • Contribution of genetic factors for melanoma susceptibility ...
    One MM patient with a family history of MM, who had developed other skin cancers, was homozygous for a novel TYR variant (P406L) of unknown significance. ...
    www.ncbi.nlm.nih.gov/pubmed/19320745
  • Contribution of genetic factors for melanoma susceptibility ...
    The associated TYR R402Q variant (rs1126809*A) was found in 29% of cases, similar to what ... homozygous for a novel TYR variant (P406L) of unknown significance. ...
    www3.interscience.wiley.com/journal/122241812/abstract
  • Albinism: Gene Mutations in Patients with Oculocutaneous ...
    Tyr. p. Trp1. SLC45A2. Melanocyte Proteins. Tyr (OCA1) tyrosine. amino acid ... P406L. G419R. P431L. G446S. D448N. Missense Mutations. S50X. 286insA. 344delGA. R116X. W178X ...
    www.mostgene.org/2009_conference/Brilliant_albinism.pdf
  • Tyrosinase Mutations
    P406L. c.1217C>T. p.Pro406Leu. EX4. B. Caucasian .0006. Giebel et al. ... type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR gene. ...
    albinismdb.med.umn.edu/oca1mut.html
  • Detection of 53 Novel DNA Variations Within the Tyrosinase ...
    gene (TYR) resulting in OCA1. Analysing patients with recessively ... OCA genes have been identified including the tyrosinase gene (TYR, MIM# 606933; ...
    www.albinismus.info/literatur/hummutat_oca.pdf
  • Novel and recurrent mutations in the tyrosinase gene and the ...
    R403S, and P406L eliminate HaeIII, MboI, BanI, and MnlI re ... R403S, and P406L mutations demonstrating. that the A355P and P406L mutations segregate on ...
    www.albinismus.info/literatur/AlbiPuibmitWeber.pdf
  • Melanoma Genetics - Washington University, Department of ...
    NewsRx is the leading source of news and information on Melanoma Genetics ... MM, who had developed other skin cancers, was homozygous for a novel TYR variant ...
    newsrx.com/newsletters/.../2009-05-05/1105052009511CW.html
  • Helms, C (Cynthia)
    The associated TYR R402Q variant (rs1126809*A) was found in 29% of cases, similar to what ... homozygous for a novel TYR variant (P406L) of unknown significance. ...
    lib.bioinfo.pl/auid:2124001
  • EPOS - European Paediatric Ophthalmological Society
    Mutations in the single heterozygous state could be shown in OA (1 TYR + 1 P) and OCA (3 TYR + 13 P). R402Q and P406L were the most prevalent mutations in TYR. ...
    www.epos-focus.org/meeting/2007/showabstract.php?id=803076

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 6

Edit history
 

Gene search

"GENE" or "GENE A123C":

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