Submissions for variant NM_152443.3(RDH12):c.210dup (p.Arg71fs)

gnomAD frequency: 0.00001  dbSNP: rs797044761

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000330650	SCV000331697	pathogenic	not provided	2014-10-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001067765	SCV001232844	pathogenic	Leber congenital amaurosis 13	2024-10-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg71Glnfs*12) 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). This variant is present in population databases (rs551914133, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 30902645). ClinVar contains an entry for this variant (Variation ID: 197878). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001073904	SCV001239469	likely pathogenic	Retinal dystrophy	2018-05-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001067765	SCV004208597	pathogenic	Leber congenital amaurosis 13	2024-02-10	criteria provided, single submitter	clinical testing
3billion	RCV001067765	SCV005904870	pathogenic	Leber congenital amaurosis 13	2024-01-23	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000197878 /PMID: 30902645 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Natera, Inc.	RCV001826911	SCV002091257	pathogenic	Leber congenital amaurosis	2021-03-25	no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV001067765	SCV004228926	not provided	Leber congenital amaurosis 13		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 02-25-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.