Submissions for variant NM_152443.3(RDH12):c.63_66del (p.Ile22fs)

dbSNP: rs794729650

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000596926	SCV000705360	likely pathogenic	not provided	2017-01-09	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001074407	SCV001239989	likely pathogenic	Retinal dystrophy	2019-08-10	criteria provided, single submitter	clinical testing
Invitae	RCV000185560	SCV001376252	pathogenic	Leber congenital amaurosis 13	2023-07-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant is also known as Ile22Gly. This premature translational stop signal has been observed in individual(s) with autosomal recessive early onset retinal disease (PMID: 30372751). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile22Glyfs*19) in the RDH12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RDH12 are known to be pathogenic (PMID: 17964524, 22065924, 32014858, 34001834).
Baylor Genetics	RCV000185560	SCV004208588	pathogenic	Leber congenital amaurosis 13	2023-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000596926	SCV005080179	pathogenic	not provided	2023-12-07	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17964524, 30372751, 22065924, 36284670, 24154662)
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000185560	SCV000238448	likely pathogenic	Leber congenital amaurosis 13	2015-02-17	no assertion criteria provided	research	This variant (c.63_66del; p.Ile22Glyfs*19) has been previously published in a cohort with LCA in one individual (PMID: 17964524) and results in a premature stop 19 amino acids later. The resulting product being severely truncated and less than 1/3 of the expected length. This variant is not seen in the ExAC database nor in the ClinVar database.
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000185560	SCV000536762	likely pathogenic	Leber congenital amaurosis 13	2015-02-17	no assertion criteria provided	research