ClinVar Miner

Submissions for variant NM_000311.5(PRNP):c.628G>A (p.Val210Ile) (rs74315407)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532969 SCV000644931 pathogenic Huntington disease-like 1 2017-06-13 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 210 of the PRNP protein (p.Val210Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs74315407, ExAC 0.003%). This variant has been reported in many cases of sporadic and familial Creutzfeldt-Jakob disease (CJD) (PMID: 26268049, 26578040, 24583440, 10526198, 7902693). In several cases, this variant has also been identified in unaffected family members, indicating that it is an incompletely penetrant allele (PMID: 26791950, 10526198, 7902693). A large case control study confirmed this finding, and reported that individuals carrying this variant have a life-time risk of developing prion disease of approximately 10% (PMID: 26791950). ClinVar contains an entry for this variant (Variation ID: 13403). Experimental studies have shown that this missense change leads to functional and structural changes in the PRNP protein (PMID: 21839748, 21909425, 22947063, 10079068, 14761942). In addition, mice with a chimeric human–mouse PRNP transgene that were inoculated with brain extract from affected individuals carrying this variant developed prion disease (PMID: 11756597). In summary, this variant is reported to cause CJD. However, as this variant is associated with a lower penetrance than other pathogenic alleles in the PRNP gene, it has been classified as Pathogenic (low penetrance).
OMIM RCV000014342 SCV000034591 pathogenic Jakob-Creutzfeldt disease 1999-10-15 no assertion criteria provided literature only
GeneReviews RCV000020255 SCV000040609 pathologic Genetic prion diseases 2008-12-18 no assertion criteria provided curation Converted during submission to Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.