ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.11374C>T (p.Arg3792Ter)

dbSNP: rs565203731
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000411243 SCV000699370 pathogenic Charlevoix-Saguenay spastic ataxia 2017-02-23 criteria provided, single submitter clinical testing Variant summary: The SACS c.11374C>T (p.Arg3792X) variant results in a premature termination codon, predicted to cause a truncated or absent SACS protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Mutation taster predicts a damaging outcome for this variant. This variant is absent in 121060 control chromosomes while it was reported in multiple ARSACS patients indicating causality. In addition a clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Paris Brain Institute, Inserm - ICM RCV000411243 SCV001451191 pathogenic Charlevoix-Saguenay spastic ataxia criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001310676 SCV001500568 pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000411243 SCV002027623 pathogenic Charlevoix-Saguenay spastic ataxia 2021-09-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV000411243 SCV004209977 pathogenic Charlevoix-Saguenay spastic ataxia 2023-05-31 criteria provided, single submitter clinical testing
Invitae RCV003766121 SCV004670737 pathogenic Spastic paraplegia 2023-11-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3792*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 788 amino acid(s) of the SACS protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 18569450, 31743419, 33624863). ClinVar contains an entry for this variant (Variation ID: 370283). This variant disrupts a region of the SACS protein in which other variant(s) (p.Asn4549Asp) have been determined to be pathogenic (PMID: 15156359, 21507954). 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.
Counsyl RCV000411243 SCV000485547 likely pathogenic Charlevoix-Saguenay spastic ataxia 2016-01-05 no assertion criteria provided clinical testing
Natera, Inc. RCV000411243 SCV002086152 pathogenic Charlevoix-Saguenay spastic ataxia 2020-09-11 no assertion criteria provided clinical testing

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