Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000364271 | SCV000329748 | pathogenic | not provided | 2018-09-20 | criteria provided, single submitter | clinical testing | The R1606X pathogenic variant in the SETX gene has been reported previously in combination with a second SETX variant in two unrelated individuals with ataxia, oculomotor apraxia, cerebellar dysarthria, neuropathy with muscular atrophy, areflexia of upper and lower limbs, and eleveated serum AFP (Bernard et al., 2009). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1606X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R1606X as a pathogenic variant. |
Labcorp Genetics |
RCV002518808 | SCV003290433 | pathogenic | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1606*) in the SETX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SETX are known to be pathogenic (PMID: 14770181). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with clinical features of autosomal recessive spinocerebellar ataxia (PMID: 19744353, 33956305). ClinVar contains an entry for this variant (Variation ID: 280027). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV003233534 | SCV003931358 | pathogenic | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2023-02-08 | criteria provided, single submitter | clinical testing |