Submissions for variant NM_003748.4(ALDH4A1):c.512G>A (p.Arg171Gln)

gnomAD frequency: 0.00001  dbSNP: rs767459105

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001338465	SCV001532132	uncertain significance	Hyperprolinemia type 2	2020-03-03	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ALDH4A1-related conditions. This variant is present in population databases (rs767459105, ExAC 0.006%). This sequence change replaces arginine with glutamine at codon 171 of the ALDH4A1 protein (p.Arg171Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine.
CeGaT Center for Human Genetics Tuebingen	RCV001815540	SCV002062411	uncertain significance	not provided	2021-11-01	criteria provided, single submitter	clinical testing