ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.6434T>A (p.Leu2145Ter) (rs770490672)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000850593 SCV000992819 pathogenic Charlevoix-Saguenay spastic ataxia 2017-12-31 criteria provided, single submitter clinical testing
Invitae RCV001386982 SCV001587445 pathogenic Spastic paraplegia 2020-08-20 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SACS gene (p.Leu2145*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2435 amino acids of the SACS protein. This variant is present in population databases (rs770490672, ExAC 0.003%). This variant has not been reported in the literature in individuals with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 689782). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Arg3903*) have been determined to be pathogenic (PMID: 19892370, 21745802). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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