ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.242G>T (p.Arg81Ile) (rs1429137932)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cytogenetics and Genomics Laboratory,Medical University of South Carolina RCV000754977 SCV000803387 likely pathogenic Leber congenital amaurosis 2018-06-01 criteria provided, single submitter research
Invitae RCV001053470 SCV001217734 pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2019-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with isoleucine at codon 81 of the RPE65 protein (p.Arg81Ile). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Leber congenital amaurosis in families (PMID: 30870047). ClinVar contains an entry for this variant (Variation ID: 559523). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV001098872 SCV001255269 uncertain significance Leber congenital amaurosis 2 2018-02-16 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001098873 SCV001255270 uncertain significance Retinitis pigmentosa 2018-02-16 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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