ClinVar Miner

Submissions for variant NM_001371279.1(REEP1):c.512del (p.Pro171fs) (rs387906263)

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 RCV000001936 SCV000553161 likely pathogenic Spastic paraplegia 31, autosomal dominant 2016-08-08 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 6 of the REEP1 mRNA (c.512delC), causing a frameshift at codon 171. This creates a new translational stop signal in the last exon of the REEP1 mRNA and extends the coding sequence by 20 amino acids (p.Pro171Hisfs*52). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 31 amino acids and replace with 51 in correct amino acids. Loss-of-function variants in REEP1 are known to be pathogenic. This particular variant has been reported to co-segregate with disease in a family affected with hereditary spastic paraplegia (PMID: 16826527). This variant is also known as c.507delC in the literature. ClinVar contains an entry for this variant (Variation ID: 1859). A different variant (c.537_540del) downstream of this variant (c.512delC) that also causes a frameshift and coding sequence extension was reported to be pathogenic in an individual affected with hereditary spastic paraplegia (PMID: 18321925). In summary, this is a rare frameshift and extension that has been reported to co-segregate with disease in one family. In addition, a downstream variant resulting in a similar protein sequence change was reported in an affected individual. However, without additional genetic or functional evidence, this variant has been classified as Likely Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000001936 SCV000778432 pathogenic Spastic paraplegia 31, autosomal dominant 2017-05-17 criteria provided, single submitter clinical testing
OMIM RCV000001936 SCV000022094 pathogenic Spastic paraplegia 31, autosomal dominant 2006-08-01 no assertion criteria provided literature only

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.