Submissions for variant NM_025114.4(CEP290):c.1667T>A (p.Ile556Asn)

gnomAD frequency: 0.00012  dbSNP: rs727503854

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723757	SCV000202419	uncertain significance	not provided	2016-03-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000152978	SCV000715241	likely benign	not specified	2017-01-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001058824	SCV001223420	uncertain significance	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 556 of the CEP290 protein (p.Ile556Asn). This variant is present in population databases (rs727503854, gnomAD 0.2%). This missense change has been observed in individual(s) with CEP290-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 166836). 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 expected to disrupt CEP290 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc.	RCV001275036	SCV001459790	likely benign	Leber congenital amaurosis	2020-04-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532719	SCV004752303	likely benign	CEP290-related disorder	2022-03-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).