Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000440159 | SCV000514610 | pathogenic | not provided | 2019-05-28 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32536663) |
| Invitae | RCV001861495 | SCV002184790 | uncertain significance | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2021-07-28 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SETX protein function. ClinVar contains an entry for this variant (Variation ID: 378574). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with methionine at codon 8 of the SETX protein (p.Thr8Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. |