COL9A3 R103W - GET-Evidence

Curation:
Currentness:

COL9A3 R103W

(COL9A3 Arg103Trp)


Short summary

Carriers of this collagen variant are associated with having a significantly increased risk of lumbar disc disease (~11% total risk compared to a typical risk of 4%).

Variant evidence
Computational 2

NBLOSUM = 4, similar diseases associated with mutations in this gene.

Functional -
Case/Control 5

p=0.000028

See Paassilta P et al. 2001 (11308397).

Familial

No familial evidence.

 
Clinical importance
Severity 3

Causes pain

Treatability 2

Except in severe cases treatment is usually rest & pain relief. Prophylactic behavioral modification may help.

Penetrance 3

7.3% increased attributable risk.

See Paassilta P et al. 2001 (11308397).

 

Impact

Moderate clinical importance, Likely pathogenic

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

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr20:61451332: 4.8% (517/10758) in EVS
  • T @ chr20:60921776: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 4.8% (517/10758)

Publications
 

Paassilta P, Lohiniva J, Göring HH, Perälä M, Räinä SS, Karppinen J, Hakala M, Palm T, Kröger H, Kaitila I, Vanharanta H, Ott J, Ala-Kokko L. Identification of a novel common genetic risk factor for lumbar disk disease. JAMA. 2001 Apr 11;285(14):1843-9. PubMed PMID: 11308397.

In a screen for mutations in collagen genes with lumbar disc disease this variant was found to be significantly associated with the disease.

Of 171 patients, 2 were homozygous for this variant and 38 were heterozygous. In 186 healthy controls there were no homozygotes and 15 heterozygotes. Counting alleles, this is case+: 42, case-: 300, control+: 15, control-: 357, and a two-tailed Fisher’s Exact test gives p=0.000048. The authors include some other patients (primary osteoarthritis, rheumatoid arthritis, chondrodysplasias) to get a p-value of 0.000028 with the same statistical test.

The incidence of lumbar disc disease in carriers of this variant is increased 2.7x compared to non-carriers (11.6% vs. 4.3%), an increased attributable risk of 7.3%.

Genomes
 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het T @ chr20:61451332

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het T @ chr20:61451332

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het T @ chr20:61451332

 

GS10851 - var-GS10851-1100-36-ASM
het T @ chr20:60921777

 

Other external references
 

    dbSNP
  • rs61734651
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    Web search results (10 hits -- see all)
  • Mendelian Inheritance in Man Document Reader
    Genetic linkage to the COL9A3 locus on chromosome 20q13.3 was ... They found an arg103-to-trp (R103W) substitution in the COL9A3 gene; the authors referred to the mutant ...
    www.angis.org.au/bin/Databases/BIRX/birx_doc?phtomim+120270
  • A Mutation in COL9A1 Causes Multiple Epiphyseal Dysplasia ...
    Recombination was observed between COL9A1, COL9A2, COL9A3, and COMP and the MED phenotype ... COL9A3: 5. 324CrT. R103W. 5/65. 7/93. 5. 325GrA. R103Q. 1/69. 1/99. 17. 904CrT ...
    www.twinsuk.ac.uk/Publicatons/2001/Czarny. AJG.pdf
  • Gemeinschaftspraxis für Humangenetik
    Bandscheibenvorfall (Intervertebral Disc Disease, IDD; COL9A2 p.Q326W, COL9A3 p.R103W) Ehlers-Danlos-Syndrom Typ VII A und B (Arthrochalasetyp; COL1A1, COL1A2) ...
    medizinische-genetik-dresden.de/liste/Diagnostikliste.pdf
  • Type III 98%
    ... germ cell tumor 9989495 COL9A3 Q14050 R103W 105 VAR_026468 CAMKL (0. ... 11173845 11781872 9677057 NEIL2 Q969S2 R103W 101 VAR_020587 CAMKL (0.722) PKC ...
    nih.go.kr/phosphovariant/html/family_whole/TypeIII_98.txt
  • Type III 95%
    Gene name SWISS-PROT ID Variant site Phosphorylation site SWISS-PROT ... gruop(s) Added kinase family(s) Removed kinase gruop(s) Removed kinase family(s) ...
    www.nih.go.kr/phosphovariant/html/group_whole/TypeIII_95.txt
  • OMIM: 120270
    Genetic linkage to the COL9A3 locus on chromosome 20q13.3 was ... They found an arg103-to-trp (R103W) substitution in the COL9A3 gene; the authors referred to the mutant ...
    www.genome.jp/dbget-bin/www_bget?omim+120270
  • BILATERAL HEREDITARY MICRO-EPIPHYSEAL DYSPLASIA
    positional and functional candidate gene COL9A3 showed an A-to-T conversion at ... Arg103Trp (R103W) substitution to be associated with disease cases when ...
    igitur-archive.library.uu.nl/dissertations/.../c3.pdf
  • BILATERAL HEREDITARY MICRO-EPIPHYSEAL DYSPLASIA
    positional and functional candidate gene COL9A3 showed an A-to-T conversion at ... Arg103Trp (R103W) substitution to be associated with disease cases when ...
    igitur-archive.library.uu.nl/dissertations/.../full.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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