ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.961C>T (p.Arg321Ter)

dbSNP: rs1175545518
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671337 SCV000796300 pathogenic Charlevoix-Saguenay spastic ataxia 2017-12-11 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001090243 SCV001245662 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing SACS: PVS1, PM2, PM3, PS4:Supporting
Athena Diagnostics RCV001090243 SCV001880442 pathogenic not provided 2021-05-26 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000671337 SCV002014997 pathogenic Charlevoix-Saguenay spastic ataxia 2021-10-20 criteria provided, single submitter clinical testing Variant summary: SACS c.961C>T (p.Arg321X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251410 control chromosomes (gnomAD). c.961C>T has been reported in the literature in individuals affected with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay (Vermeer_2008, Prodi_2013). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000671337 SCV002027671 pathogenic Charlevoix-Saguenay spastic ataxia 2021-09-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001868253 SCV002238298 pathogenic Spastic paraplegia 2021-06-04 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg321*) in the SACS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SACS are known to be pathogenic (PMID: 18465152, 20876471). This variant has been observed in individual(s) with SACS-related conditions (PMID: 18465152). ClinVar contains an entry for this variant (Variation ID: 555502). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000671337 SCV004209983 pathogenic Charlevoix-Saguenay spastic ataxia 2023-11-20 criteria provided, single submitter 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.