Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Centre for Mendelian Genomics, |
RCV001198042 | SCV001368827 | likely pathogenic | Cutis laxa, autosomal dominant 3 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3,PP5. |
| Labcorp Genetics |
RCV003765291 | SCV002315928 | likely pathogenic | Cutis laxa, autosomal dominant 3; Autosomal dominant spastic paraplegia type 9; de Barsy syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 715 of the ALDH18A1 protein (p.Asp715His). This variant is present in population databases (rs752669339, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 26026163). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217115). 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 ALDH18A1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| OMIM | RCV000200955 | SCV000255597 | pathogenic | Autosomal recessive complex spastic paraplegia type 9B | 2015-08-21 | no assertion criteria provided | literature only |