Submissions for variant NM_152443.3(RDH12):c.481C>T (p.Arg161Trp)

gnomAD frequency: 0.00002  dbSNP: rs759408031

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000797267	SCV000936816	pathogenic	Leber congenital amaurosis 13	2023-12-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 161 of the RDH12 protein (p.Arg161Trp). This variant is present in population databases (rs759408031, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive RDH12-related conditions (PMID: 22065924, 27032803; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 643541). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RDH12 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000797267	SCV004208555	likely pathogenic	Leber congenital amaurosis 13	2023-10-28	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003889988	SCV004707752	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV002267742	SCV001161225	pathogenic	Cone-rod dystrophy	2019-06-23	no assertion criteria provided	research
Natera, Inc.	RCV001277204	SCV001464103	likely pathogenic	Leber congenital amaurosis	2020-09-16	no assertion criteria provided	clinical testing