ClinVar

Description

The c.9537_9541delATTGA variant in the SACS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.9537_9541delATTGA variant causes a frameshift starting with codon Glutamic acid 3179, changes this amino acid to an Aspartic acid residue, and creates a premature Stop codon at position 17 of the new reading frame, denoted p.Glu3179AspfsX17. This variant replaces the last 1401 amino acids by 16 incorrect residues and is predicted to cause loss of normal protein function through protein truncation. Additionally, protein truncating pathogenic variants downstream of this variant have been reported in the Human Gene Mutation Database in association with SACS-related disorders (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. The c.9537_9541delATTGA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.9537_9541delATTGA as a likely pathogenic variant.