Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genome Diagnostics Laboratory, |
RCV001848373 | SCV002104517 | uncertain significance | Hereditary spastic paraplegia | 2020-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003772378 | SCV004606186 | uncertain significance | Cutis laxa, autosomal dominant 3; Autosomal dominant spastic paraplegia type 9; de Barsy syndrome | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 244 of the ALDH18A1 protein (p.Lys244Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALDH18A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1344270). 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 ALDH18A1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |