ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.12232C>T (p.Arg4078Ter)

dbSNP: rs141315518
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169220 SCV000220485 likely pathogenic Charlevoix-Saguenay spastic ataxia 2014-07-07 criteria provided, single submitter literature only
Labcorp Genetics (formerly Invitae), Labcorp RCV001850393 SCV002174456 pathogenic Spastic paraplegia 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg4078*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 502 amino acid(s) of the SACS protein. This variant is present in population databases (rs141315518, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with spastic ataxia of Charlevoix-Saguenay (PMID: 22816526). ClinVar contains an entry for this variant (Variation ID: 188867). This variant disrupts a region of the SACS protein in which other variant(s) (p.Tyr4538* ) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002509271 SCV002819085 likely pathogenic not provided 2022-07-06 criteria provided, single submitter clinical testing Reported in an individual with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), however segregation information was not provided (Prodi et al., 2013); Nonsense variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22816526, 31589614)
Baylor Genetics RCV000169220 SCV004202281 pathogenic Charlevoix-Saguenay spastic ataxia 2024-03-24 criteria provided, single submitter clinical testing

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