Submissions for variant NM_002860.4(ALDH18A1):c.408C>A (p.Ser136Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003774999	SCV002590648	likely pathogenic	Cutis laxa, autosomal dominant 3; Autosomal dominant spastic paraplegia type 9; de Barsy syndrome	2022-11-25	criteria provided, single submitter	clinical testing	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ALDH18A1 protein function. This missense change has been observed in individual(s) with clinical features of autosomal dominant ALDH18A1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 136 of the ALDH18A1 protein (p.Ser136Arg).