Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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, |
RCV001544509 | SCV001762420 | pathogenic | Ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and intellectual disability | criteria provided, single submitter | clinical testing | ||
Genome- |
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 |