ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.4232T>G (p.Leu1411Ter)

dbSNP: rs867249938
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521561 SCV000618805 pathogenic not provided 2022-05-27 criteria provided, single submitter clinical testing 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: 27533158, 23250129, 32606552)
Invitae RCV001064306 SCV001229198 pathogenic Spastic paraplegia 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1411*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3169 amino acid(s) of the SACS protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive spastic ataxia of Charlevoix-Saguenay (PMID: 32606552). ClinVar contains an entry for this variant (Variation ID: 450250). This variant disrupts a region of the SACS protein in which other variant(s) (p.Arg3903*) have been determined to be pathogenic (PMID: 19892370, 21745802). 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.
Genome-Nilou Lab RCV000984213 SCV002027660 pathogenic Charlevoix-Saguenay spastic ataxia 2021-09-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV000984213 SCV004209889 pathogenic Charlevoix-Saguenay spastic ataxia 2023-10-13 criteria provided, single submitter clinical testing
Counsyl RCV000984213 SCV001132281 likely pathogenic Charlevoix-Saguenay spastic ataxia 2019-01-24 no assertion criteria provided clinical testing

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