ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.7273C>T (p.Arg2425Ter) (rs145766983)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599123 SCV000710509 pathogenic not provided 2018-10-01 criteria provided, single submitter clinical testing The R2425X variant in the SACS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The R2425X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R2425X as a pathogenic variant.
Invitae RCV000704868 SCV000833839 pathogenic Spastic paraplegia 2017-06-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SACS gene (p.Arg2425*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 2154 amino acids of the SACS protein. This variant is present in population databases (rs145766983, ExAC 0.01%). This variant has not been reported in the literature in individuals with a SACS-related disease. ClinVar contains an entry for this variant (Variation ID: 370415). A different truncation downstream of this variant (p.Ile2949Phefs*4) has been determined to be pathogenic (PMID: 23250129). This suggests that deletion of this region of the SACS protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000412060 SCV000485731 likely pathogenic Spastic ataxia Charlevoix-Saguenay type 2016-02-04 no assertion criteria provided clinical testing

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