Submissions for variant NM_003748.4(ALDH4A1):c.658G>C (p.Ala220Pro)

dbSNP: rs778113718

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000791062	SCV000930331	uncertain significance	not specified	2019-04-27	criteria provided, single submitter	clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV002477796	SCV002770432	uncertain significance	Hyperprolinemia type 2	2020-08-31	criteria provided, single submitter	research	Two heterozygous variants, a 8 base pair duplication c.363_370dup (p.Arg124LeufsTer9) in exon 5 and a missense variant c.658G>C (p.Ala220P) in exon 7 of the ALDH4A1 gene were identified. The variant c.363_370dup was not observed in the 1000 genomes and gnomAD databases. The variant c.658G>C was not observed in the 1000Genomes but has a MAF of 0.003% in the gnomAD database. The in silico prediction of the variant c.363_370dup is damaging by MutationTaster2 and for the variant c.658G>C is damaging by LRT and MutationTaster2. The variant c.658G>C lies in the aldehyde dehydrogenase domain of the ALDH4A1 protein. The reference region are conserved across species. In summary, the variant c.363_370dup and c.658G>C meets our criteria to be classified as likely pathogenic and a variant of uncertain significance, respectively.