ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.11100dup (p.Trp3701fs)

dbSNP: rs1883571351
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195303 SCV001365625 likely pathogenic Autosomal recessive spastic ataxia 2019-04-15 criteria provided, single submitter clinical testing The p.Trp3701MetfsX17 variant in SACS has not been previously reported in individuals with spastic ataxia and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 3701 and leads to a premature termination codon 17 amino acids downstream. This termination codon occurs within the last exon and is, therefore, likely to escape nonsense mediated decay (NMD) and result in a protein truncated by 860 amino acids (representing 19% of the full protein length). Notably, many other truncating variants in this region have been reported in the homozygous or compound heterozygous state in individuals with ARSACS. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive spastic ataxia, Charlevoix-Saguenay type. ACMG/AMP Criteria applied: PVS1_Strong, PM2.

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.