DSPP R68W - GET-Evidence



(DSPP Arg68Trp)

Short summary

Probably benign. One report linked this to causing dentinogenesis Imperfecta type II in a large Swedish family, but subsequent publications have observed this is a common variant and conclude it is a nonpathogenic polymorphism.

Variant evidence
Computational -1

BLOSUM100 predicts disruptive effect, other variants in the gene associated with disease. Polyphen 2 score unavailable.

Functional -
Case/Control 3

Frequency of this variant allele supports no significant pathogenic effect

See Acevedo AC et al. 2009 (18797159), unpublished research (below).

Familial -
Clinical importance
Severity -
Treatability -
Penetrance -


Low clinical importance, Uncertain benign

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

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • T @ chr4:88533540: 14.3% (1413/9878) in EVS
  • T @ chr4:88752563: 17.2% (22/128) in GET-Evidence
  • Frequency shown in summary reports: 14.3% (1413/9878)


Malmgren B, Lindskog S, Elgadi A, Norgren S. Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II. Hum Genet. 2004 Apr;114(5):491-8. Epub 2004 Feb 3. PubMed PMID: 14758537.

This variant was found segregating with Dentinogenesis Imperfecta type II in a large Swedish family. 6/14 affected and 10/56 unaffected were genotyped and the variant was shown to segregate with disease. LOD score is not reported, we calculate it to be 3.6. Controls are not reported.

Kim JW, Simmer JP. Hereditary dentin defects. J Dent Res. 2007 May;86(5):392-9. Review. PubMed PMID: 17452557.

Review article. Other variants in DSPP covered that have been reported to cause the disease.

Acevedo AC, Santos LJ, Paula LM, Dong J, MacDougall M. Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families. Cells Tissues Organs. 2009;189(1-4):230-6. Epub 2008 Sep 16. PubMed PMID: 18797159; PubMed Central PMCID: PMC2824200.

Cites Holappa et al. 2006, Hart and Hart 2007, and dbSNP data as showing allele frequencies of 6-16%, concluding “Collectively, these findings and the data present in our study suggest that this variation is a polymorphism and not a mutation associated with the pathogenesis of DGI-II.”




hu604D39 - CGI sample GS00253-DNA_B02_200_37
het T @ chr4:88533540



huE80E3D - CGI sample GS00253-DNA_D01_200_37
het T @ chr4:88533540


GS18501 - var-GS18501-1100-36-ASM
hom T @ chr4:88752564


GS18502 - var-GS18502-1100-36-ASM
het T @ chr4:88752564


GS18504 - var-GS18504-1100-36-ASM
het T @ chr4:88752564


GS18508 - var-GS18508-1100-36-ASM
het T @ chr4:88752564


GS19025 - var-GS19025-1100-36-ASM
het T @ chr4:88752564


GS19026 - var-GS19026-1100-36-ASM
het T @ chr4:88752564


GS19129 - var-GS19129-1100-36-ASM
hom T @ chr4:88752564


GS19239 - var-GS19239-1100-36-ASM
het T @ chr4:88752564


GS19240 - var-GS19240-1100-36-ASM
het T @ chr4:88752564


GS19701 - var-GS19701-1100-36-ASM
het T @ chr4:88752564


GS19703 - var-GS19703-1100-36-ASM
het T @ chr4:88752564


GS19834 - var-GS19834-1100-36-ASM
het T @ chr4:88752564


GS21767 - var-GS21767-1100-36-ASM
het T @ chr4:88752564


Other external references

  • rs36094464

Other in silico analyses

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 2

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Gene search

"GENE" or "GENE A123C":

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