ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.9305T>A (p.Leu3102Ter) (rs886041949)

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Total submissions: 5
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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 likely pathogenic Spastic paraplegia 2020-03-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SACS gene (p.Leu3102*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1478 amino acids of the SACS protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hereditary motor and sensory neuropathy (PMID: 30460542, 21507954). ClinVar contains an entry for this variant (Variation ID: 280809). This variant disrupts the p.Asn4549 amino acid residue in SACS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15156359). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Kasturba Medical College, Manipal University RCV001544509 SCV001762420 pathogenic Ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and mental retardation 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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