Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000644821 | SCV000766536 | uncertain significance | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia autosomal recessive 1 | 2017-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 223 of the SETX protein (p.Leu223Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs774068411, ExAC 0.009%). This variant has not been reported in the literature in individuals with SETX-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |