ClinVar Miner

Submissions for variant NM_014231.5(VAMP1):c.340+2T>G

dbSNP: rs878854975
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233592 SCV000289943 pathogenic Spastic paraplegia 2016-02-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the VAMP1 gene. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in many (>10) individuals affected with spastic ataxia. In addition, it has been shown to segregate with disease in 4 large families with origins in Newfoundland, Cananda (PMID: 22958904). Experimental studies have shown that this intronic change leads to aberrant splicing of intron 4, which is predicted to lead to a truncated protein product relative to the major VAMP1 neuronal isoform (PMID: 22958904). In summary, this variant has been reported to segregate with disease in affected families and to alter mRNA splicing in functional studies. For these reasons, this change has been classified as Pathogenic.
GeneDx RCV000255544 SCV000322101 pathogenic not provided 2025-01-22 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant affects a critical donor site for the splicing of VAMP1 isoforms and results in an in-frame addition of 33 amino acids (PMID: 22958904); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 27957547, 11774073, 22958904, 38355957)
Athena Diagnostics RCV000255544 SCV000844856 pathogenic not provided 2017-11-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005008203 SCV005629613 pathogenic Spastic ataxia 1; Myasthenic syndrome, congenital, 25, presynaptic 2024-01-12 criteria provided, single submitter clinical testing
OMIM RCV000128446 SCV000172127 pathogenic Spastic ataxia 1 2012-09-07 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.