NTRK1 G613V - GET-Evidence

Curation:
Currentness:

NTRK1 G613V

(NTRK1 Gly613Val)


Short summary

Also called G607V, this variant has been reported as a nonpathogenic polymorphism.

Variant evidence
Computational 1

Polyphen 2 predicts benign effect

Functional -
Case/Control 3

Seen coincidentally with causal mutation in a case, and seen in controls

See Mardy S et al. 1999 (10330344), Mardy S et al. 2001 (11159935).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

Listed as a polymorphism here: http://www.molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?Context=9

Allele frequency

  • T @ chr1:156848946: 4.3% (462/10758) in EVS
  • T @ chr1:155115569: 3.1% (4/128) in GET-Evidence
  • Frequency shown in summary reports: 4.3% (462/10758)

Publications
 

Mardy S, Miura Y, Endo F, Matsuda I, Sztriha L, Frossard P, Moosa A, Ismail EA, Macaya A, Andria G, Toscano E, Gibson W, Graham GE, Indo Y. Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am J Hum Genet. 1999 Jun;64(6):1570-9. PubMed PMID: 10330344; PubMed Central PMCID: PMC1377900.

This variant is reported as Gly607Val, and occurs along with a deleterious upstream stop codon. It is likely a polymorphism that happened to co-occur in the same gene with the deleterious allele, although the authors are ambiguous on this point.

Gimm O, Greco A, Hoang-Vu C, Dralle H, Pierotti MA, Eng C. Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma. J Clin Endocrinol Metab. 1999 Aug;84(8):2784-7. PubMed PMID: 10443680.

Reports seeing this variant in some samples, but also the corresponding germ line samples (not cancer-specific mutations) and no significant difference in variant frequencies between these and control samples.

Mardy S, Miura Y, Endo F, Matsuda I, Indo Y. Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor. Hum Mol Genet. 2001 Feb 1;10(3):179-88. PubMed PMID: 11159935.

Here the authors conclude that this variant is a nonpathogenic polymorphism within particular ethnic backgrounds.

Genomes
 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het T @ chr1:156848946

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr1:156848946

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het T @ chr1:156848946

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het T @ chr1:156848946

 

Other external references
 

    dbSNP
  • rs6339
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the NTRK1 gene
    Hereditary Sensory and Autonomic Neuropathy IV
    NTRK1-Related Familial Medullary Thyroid Carcinoma
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NTRK1
    PolyPhen-2
  • Score: 0.004 (benign)
    Web search results (8 hits -- see all)
  • Table 3 Text
    ... total chromosomes genotyped MAF mean MAF stdev chromosomes genotyped ... criterion prediction score number sequences aligned prediction score divergence ...
    icr.ac.uk/research/research_sections/.../2842.txt
  • Inherited Peripheral Neuropathies
    Mutations in NTRK1 (TRKA) Name. c.[25C>T;1810C>T;1838 G>T]+[25C>T; 1810C>T; 1838 G>T] ... CIPA or HSN IV (H604Y + G613V are polymorphisms) htz/hmz. compound htz ...
    molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?...
  • Inherited Peripheral Neuropathies
    Mutations in NTRK1 (TRKA) Name. c.[574+1G>A]+[1810C>T;1838G>T;1843G>T; ... CIPA or HSN IV (H604Y + G613V are polymorphisms) htz/hmz. compound htz ...
    molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?...

Other in silico analyses
 

  • NBLOSUM100 score = 8
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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