Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704262 | SCV000833204 | uncertain significance | Infantile-onset ascending hereditary spastic paralysis | 2018-05-07 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with ALS2-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: "Deleterious"; PolyPhen-2: "Probably 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. This sequence change replaces lysine with methionine at codon 1045 of the ALS2 protein (p.Lys1045Met). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and methionine. This variant is present in population databases (rs781051642, ExAC 0.01%). |
Fulgent Genetics, |
RCV000764354 | SCV000895376 | uncertain significance | Amyotrophic lateral sclerosis type 2, juvenile; Juvenile primary lateral sclerosis; Infantile-onset ascending hereditary spastic paralysis | 2018-10-31 | criteria provided, single submitter | clinical testing |