Submissions for variant NM_014336.5(AIPL1):c.715T>C (p.Cys239Arg)

dbSNP: rs62637012

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004585988	SCV005077111	pathogenic	Leber congenital amaurosis	2024-04-21	criteria provided, single submitter	clinical testing	Variant summary: AIPL1 c.715T>C (p.Cys239Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251430 control chromosomes. c.715T>C has been reported in the literature as a homozygous genotype in multiple individuals affected with Leber Congenital Amaurosis (example, Sohocki_2000, Dharmaraj_2004). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function demonstrating severely reduced interactions with NUB1, leading to defective inhibition of FAT10-DHFR degradation (Bett_2012). The following publications have been ascertained in the context of this evaluation (PMID: 22347407, 15249368, 10615133, 17964524). ClinVar contains an entry for this variant (Variation ID: 5567). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM	RCV000005908	SCV000026090	pathogenic	Leber congenital amaurosis 4	2000-01-01	no assertion criteria provided	literature only
GeneReviews	RCV000005908	SCV000086964	not provided	Leber congenital amaurosis 4		no assertion provided	literature only
Retina International	RCV000086231	SCV000118377	not provided	not provided		no assertion provided	not provided
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV000005908	SCV001335450	pathogenic	Leber congenital amaurosis 4		no assertion criteria provided	research