Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003772924 | SCV002217726 | uncertain significance | Cutis laxa, autosomal dominant 3; Autosomal dominant spastic paraplegia type 9; de Barsy syndrome | 2020-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with isoleucine at codon 742 of the ALDH18A1 protein (p.Ser742Ile). The serine residue is highly conserved and there is a large physicochemical difference between serine and isoleucine. This variant is present in population databases (rs765567477, ExAC 0.002%). This variant has been observed in individual(s) with autosomal recessive cutis laxa (PMID: 22411858). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |