Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000539262 | SCV000645238 | uncertain significance | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2021-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, a(n) basic and polar amino acid, with methionine, a(n) neutral and non-polar amino acid, at codon 768 of the SETX protein (p.Lys768Met). 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 not expected to disrupt SETX protein function. ClinVar contains an entry for this variant (Variation ID: 468492). This variant has not been reported in the literature in individuals affected with SETX-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Prevention |
RCV003960341 | SCV004782938 | uncertain significance | SETX-related condition | 2023-10-30 | criteria provided, single submitter | clinical testing | The SETX c.2303A>T variant is predicted to result in the amino acid substitution p.Lys768Met. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |