ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.4265_4274dup (p.Ile1426_Pro1427insAlaTer) (rs1555252433)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486986 SCV000567533 pathogenic not provided 2015-07-27 criteria provided, single submitter clinical testing The c.4265_4274dup10 duplication in the SACS gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The c.4265_4274dup10 duplication causes aframeshift starting with codon Isoleucine 1426, changes this amino acid to an Alanine residue, and createsa premature Stop codon at position 2 of the new reading frame, denoted p.Ile1426AlafsX2. This variant is predicted to cause loss of normal protein function through protein truncation; it causes the deletion of thelast 3154 amino acids and an insertion of one incorrect amino acid. Protein truncating variantsdownstream of this duplication have been reported in the Human Gene Mutation Database in associationwith ARSACS (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants.The c.4265_4274dup10 duplication was not observed in approximately 6,500 individuals of European andAfrican American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. We interpret c.4265_4274dup10 as a pathogenic variant.

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