COMT V158M - GET-Evidence

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

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Curation:
Currentness:

COMT V158M

(COMT Val158Met)


Short summary

A codominant allele affecting COMT enzyme activity, considered a benign functional polymorphism.
Some claims of association with schizophrenia,
Possibly provides advantage in memory and attention tasks (“worrier strategy”).

Variant evidence
Computational 1

PolyPhen2: Benign, score 0.001
SIFT: Tolerated 0.25
GVGD: GV 30.92; GD 0.00; Class C0
Variant Effect Predictor (Ensembl):
SIFT=deleterious(0.04);
PolyPhen=benign(0.006);
Condel=deleterious(0.897)
Mutation Tasting Prediction: Polymorphism, P value: 0.999909; protein features (might be) affected.

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

  • A @ chr22:19951271: 44.8% (4823/10756) in EVS
  • A @ chr22:18331270: 39.8% (51/128) in GET-Evidence
  • Frequency shown in summary reports: 44.8% (4823/10756)

Publications
 

Chen X, Wang X, O'Neill AF, Walsh D, Kendler KS. Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families. Mol Psychiatry. 2004 Oct;9(10):962-7. PubMed PMID: 15124004.

 

Handoko HY, Nyholt DR, Hayward NK, Nertney DA, Hannah DE, Windus LC, McCormack CM, Smith HJ, Filippich C, James MR, Mowry BJ. Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia. Mol Psychiatry. 2005 Jun;10(6):589-97. PubMed PMID: 15505638.

.

Stein MB, Fallin MD, Schork NJ, Gelernter J. COMT polymorphisms and anxiety-related personality traits. Neuropsychopharmacology. 2005 Nov;30(11):2092-102. PubMed PMID: 15956988.

 

Liao SY, Lin SH, Liu CM, Hsieh MH, Hwang TJ, Liu SK, Guo SC, Hwu HG, Chen WJ. Genetic variants in COMT and neurocognitive impairment in families of patients with schizophrenia. Genes Brain Behav. 2009 Mar;8(2):228-37. doi: 10.1111/j.1601-183X.2008.00467.x. Epub 2008 Dec 12. Erratum in: Genes Brain Behav. 2010 Mar 1;9(2):256. PubMed PMID: 19077118.

 

Bodenmann S, Landolt HP. Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. Sleep. 2010 Aug;33(8):1027-35. PubMed PMID: 20815183; PubMed Central PMCID: PMC2910532.

 

Narasimhan S, Aquino TD, Multani PK, Rickels K, Lohoff FW. Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder. Psychiatry Res. 2012 Jun 30;198(1):112-5. doi: 10.1016/j.psychres.2011.12.034. Epub 2012 Mar 13. PubMed PMID: 22417933.

 

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
hom A @ chr22:19951271

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het A @ chr22:19951271

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
hom A @ chr22:19951271

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
hom A @ chr22:19951271

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het A @ chr22:19951271

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het A @ chr22:19951271

 

hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
hom A @ chr22:19951271

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het A @ chr22:19951271

 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het A @ chr22:19951271

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
hom A @ chr22:19951271

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
hom A @ chr22:19951271

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr22:19951271

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het A @ chr22:19951271

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het A @ chr22:19951271

 

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het A @ chr22:19951271

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
hom A @ chr22:19951271

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het A @ chr22:19951271

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
het A @ chr22:19951271

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr22:19951271

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het A @ chr22:19951271

 

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
hom A @ chr22:19951271

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het A @ chr22:19951271

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
hom A @ chr22:19951271

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
hom A @ chr22:19951271

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het A @ chr22:19951271

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het A @ chr22:19951271

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het A @ chr22:19951271

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
hom A @ chr22:19951271

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het A @ chr22:19951271

 

GS06985 - var-GS06985-1100-36-ASM
hom A @ chr22:18331271

 

GS06994 - var-GS06994-1100-36-ASM
hom A @ chr22:18331271

 

GS07357 - var-GS07357-1100-36-ASM
het A @ chr22:18331271

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr22:18331271

 

GS12004 - var-GS12004-1100-36-ASM
het A @ chr22:18331271

 

GS18501 - var-GS18501-1100-36-ASM
hom A @ chr22:18331271

 

GS18526 - var-GS18526-1100-36-ASM
het A @ chr22:18331271

 

GS18555 - var-GS18555-1100-36-ASM
het A @ chr22:18331271

 

GS18558 - var-GS18558-1100-36-ASM
het A @ chr22:18331271

 

GS18940 - var-GS18940-1100-36-ASM
het A @ chr22:18331271

 

GS18942 - var-GS18942-1100-36-ASM
het A @ chr22:18331271

 

GS19017 - var-GS19017-1100-36-ASM
het A @ chr22:18331271

 

GS19239 - var-GS19239-1100-36-ASM
het A @ chr22:18331271

 

GS19240 - var-GS19240-1100-36-ASM
het A @ chr22:18331271

 

GS19648 - var-GS19648-1100-36-ASM
het A @ chr22:18331271

 

GS19649 - var-GS19649-1100-36-ASM
het A @ chr22:18331271

 

GS19669 - var-GS19669-1100-36-ASM
het A @ chr22:18331271

 

GS19670 - var-GS19670-1100-36-ASM
hom A @ chr22:18331271

 

GS19735 - var-GS19735-1100-36-ASM
het A @ chr22:18331271

 

GS20502 - var-GS20502-1100-36-ASM
hom A @ chr22:18331271

 

Other external references
 

    dbSNP
  • rs4680
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 2

Edit history
 

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