ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.10906C>T (p.Arg3636Ter) (rs780247476)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000192438 SCV000485801 likely pathogenic Spastic ataxia Charlevoix-Saguenay type 2016-02-19 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000192438 SCV000248779 pathogenic Spastic ataxia Charlevoix-Saguenay type 2014-08-07 criteria provided, single submitter clinical testing
Invitae RCV000633059 SCV000754271 pathogenic Spastic paraplegia 2018-09-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SACS gene (p.Arg3636*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 944 amino acids (~20%) of the SACS protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in combination with another SACS variant in a single family affected with early-onset cerebellar ataxia (PMID: 18465152). ClinVar contains an entry for this variant (Variation ID: 212108). A different truncation (p.Arg3903*) that lies downstream of this variant has been determined to be pathogenic (PMID: 19892370, 21745802). 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.

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