Submissions for variant NM_000329.3(RPE65):c.419G>A (p.Gly140Glu) (rs1191496583)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000542372	SCV000644185	uncertain significance	Leber congenital amaurosis 2; Retinitis pigmentosa 20	2017-07-05	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with glutamic acid at codon 140 of the RPE65 protein (p.Gly140Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with inherited retinal dystrophy (PMID: 28181551). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Cytogenetics and Genomics Laboratory,Medical University of South Carolina	RCV000754974	SCV000803384	likely pathogenic	Leber congenital amaurosis	2018-06-01	criteria provided, single submitter	research

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