ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.5151del (p.Lys1717fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001216711 SCV001388521 pathogenic Spastic paraplegia 2019-06-06 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SACS gene (p.Lys1717Asnfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2863 amino acids 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 the literature in individuals affected with autosomal recessive spastic ataxia of Charlevoix–Saguenay or Hirschsprung disease (PMID: 26288984, 29093530). This variant is also known as c.4710delA in the literature. This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Lys2931Asnfs*22, p.Ile2949Phefs*4, p.3903*) have been determined to be pathogenic (PMID: 15486997, 11788093, 10655055, 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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