Submissions for variant NM_002860.4(ALDH18A1):c.232G>A (p.Gly78Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003777571	SCV003518138	uncertain significance	Cutis laxa, autosomal dominant 3; Autosomal dominant spastic paraplegia type 9; de Barsy syndrome	2022-11-12	criteria provided, single submitter	clinical testing	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. 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. This variant has not been reported in the literature in individuals affected with ALDH18A1-related conditions. This variant is present in population databases (rs762588270, gnomAD 0.007%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 78 of the ALDH18A1 protein (p.Gly78Ser).
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV003314750	SCV004014788	likely pathogenic	Cutis laxa, autosomal dominant 3	2023-04-12	criteria provided, single submitter	clinical testing