ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.7205_7206del (p.Leu2402fs) (rs773182375)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531534 SCV000629480 pathogenic Spastic paraplegia 2017-10-17 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 10 of the SACS mRNA (c.7205_7206delTT), causing a frameshift at codon 2402. This creates a premature translational stop signal in the last exon of the SACS mRNA (p.Leu2402Argfs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2178 amino acids of the SACS protein. This variant is present in population databases (rs773182375, ExAC 0.006%) but has not been reported in the literature in individuals with a SACS-related disease. A different truncation downstream of this variant (p.Arg3903*) 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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