ClinVar

Description

Variant summary: SACS c.7276C>T (p.Arg2426X) 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 was absent in 250002 control chromosomes. c.7276C>T has been reported in the literature in individuals affected or suspected to be affected with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay (e.g. Baets_2010, Lee_2014, Shakya_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories cited the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.