ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.9305T>A (p.Leu3102Ter)

gnomAD frequency: 0.00001  dbSNP: rs886041949
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000377502 SCV000330759 pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing The L3102X pathogenic variant in the SACS gene has not been reported previously as a pathogenic variant nor as abenign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through proteintruncation. The L3102X variant was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. We interpret L3102X as a pathogenic variant.
Fulgent Genetics, Fulgent Genetics RCV000762910 SCV000893321 pathogenic Charlevoix-Saguenay spastic ataxia 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001379554 SCV001577377 pathogenic Spastic paraplegia 2022-09-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 280809). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary motor and sensory neuropathy (PMID: 21507954, 30460542, 31692161). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu3102*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1478 amino acid(s) of the SACS protein.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV001544509 SCV001762420 pathogenic Ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and intellectual disability criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000762910 SCV002027631 pathogenic Charlevoix-Saguenay spastic ataxia 2021-09-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV000762910 SCV004202311 pathogenic Charlevoix-Saguenay spastic ataxia 2022-02-16 criteria provided, single submitter clinical testing
Counsyl RCV000762910 SCV001132280 likely pathogenic Charlevoix-Saguenay spastic ataxia 2015-06-16 no assertion criteria provided clinical testing

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