ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1496G>A (rs878854991)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 17
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230990 SCV000290034 pathogenic Spastic paraplegia 4, autosomal dominant 2020-09-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 499 of the SPAST protein (p.Arg499His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This sequence change has been reported in multiple individuals and families affected with spastic paraplegia (PMID: 16009769, 18701882, 20562464, 16682546, 16055926, 25045380, 10610178). ClinVar contains an entry for this variant (Variation ID: 240950). This amino acid substitution falls in the central ATPase domain of spastin (AAA domain) involved in ATP hydrolysis, where most sequence changes reported to cause spastic paraplegia cluster (PMID: 18701882). A different amino acid substitution at this position (Arg499Cys), also reported in spastic paraplegia patients (PMID: 11309678, 11809724, 10699187, 12161613, 16055926), has been shown to abolish spastin ATPase activity (PMID: 15716377). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000713467 SCV000339060 uncertain significance not provided 2016-01-29 criteria provided, single submitter clinical testing
Institute of Human Genetics, Klinikum rechts der Isar RCV000230990 SCV000680389 pathogenic Spastic paraplegia 4, autosomal dominant 2017-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623007 SCV000741401 likely pathogenic Inborn genetic diseases 2016-03-17 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000230990 SCV000743204 pathogenic Spastic paraplegia 4, autosomal dominant 2017-07-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000230990 SCV000745629 pathogenic Spastic paraplegia 4, autosomal dominant 2016-10-14 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000713467 SCV000844078 pathogenic not provided 2017-02-21 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,BC Children's and BC Women's Hospitals RCV000230990 SCV000898159 pathogenic Spastic paraplegia 4, autosomal dominant 2018-08-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV000230990 SCV000992839 pathogenic Spastic paraplegia 4, autosomal dominant 2017-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000230990 SCV001135658 pathogenic Spastic paraplegia 4, autosomal dominant 2019-05-28 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000230990 SCV001429163 pathogenic Spastic paraplegia 4, autosomal dominant 2016-06-17 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed).
National Institute of Neuroscience,National Center of Neurology and Psychiatry RCV000230990 SCV001438322 pathogenic Spastic paraplegia 4, autosomal dominant criteria provided, single submitter research
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000713467 SCV001446399 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Paris Brain Institute,Inserm - ICM RCV000230990 SCV001450999 pathogenic Spastic paraplegia 4, autosomal dominant criteria provided, single submitter clinical testing
Neurogenetics Laboratory,GH Pitie Salpetriere APHP RCV000230990 SCV001481803 likely pathogenic Spastic paraplegia 4, autosomal dominant criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000713467 SCV001715442 pathogenic not provided 2019-05-12 criteria provided, single submitter clinical testing PS4, PM1, PM2, PM5, PM6, PP1
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000230990 SCV001133115 pathogenic Spastic paraplegia 4, autosomal dominant 2019-09-26 no assertion criteria provided clinical testing

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.