ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.434C>G (p.Ser145Ter)

gnomAD frequency: 0.00001  dbSNP: rs994374354
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000819151 SCV000959795 pathogenic Spastic paraplegia 2024-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser145*) in the SACS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SACS are known to be pathogenic (PMID: 18465152, 20876471). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 661678). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000992789 SCV001145333 likely pathogenic not provided 2019-07-08 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Frequency data from large databases are of low quality and therefore uninformative.
Genome-Nilou Lab RCV001785730 SCV002027676 likely pathogenic Charlevoix-Saguenay spastic ataxia 2021-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001785730 SCV002811452 likely pathogenic Charlevoix-Saguenay spastic ataxia 2021-07-22 criteria provided, single submitter clinical testing
GeneDx RCV000992789 SCV003194935 pathogenic not provided 2023-01-17 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay 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: 35303589)
PreventionGenetics, part of Exact Sciences RCV003396439 SCV004104543 likely pathogenic SACS-related disorder 2023-06-02 criteria provided, single submitter clinical testing The SACS c.434C>G variant is predicted to result in premature protein termination (p.Ser145*). To our knowledge, this variant has not been reported in affected individuals. This variant is reported in 0.0065% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-23939328-G-C). Nonsense variants in SACS are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics RCV001785730 SCV004209924 pathogenic Charlevoix-Saguenay spastic ataxia 2023-08-27 criteria provided, single submitter clinical testing

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