ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.4877_4880del (p.Gly1626fs) (rs757872635)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670743 SCV000795637 likely pathogenic Spastic ataxia Charlevoix-Saguenay type 2017-11-12 criteria provided, single submitter clinical testing
GeneDx RCV000282747 SCV000330136 pathogenic not provided 2016-02-01 criteria provided, single submitter clinical testing The c.4877_4880delGCTG pathogenic variant in the SACS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.4877_4880delGCTG variant causes a frameshift starting with codon Glycine 1626, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Gly1626ValfsX5. This variant causes the last 2954 amino acids to be replaced by 4 incorrect amino acids, which is predicted to cause loss of normal protein function through protein truncation. Protein truncating pathogenic variants downstream of this variant have been reported in the Human Gene Mutation Database in association with spastic ataxia, Charlevoix-Saguenay type (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. The c.4877_4880delGCTG 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. Therefore, we interpret c.4877_4880delGCTG as a pathogenic variant.

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