ClinVar Miner

Submissions for variant NM_014336.5(AIPL1):c.265T>C (p.Cys89Arg)

gnomAD frequency: 0.00001  dbSNP: rs1264794214
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000696451 SCV000825014 pathogenic Leber congenital amaurosis 4 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 89 of the AIPL1 protein (p.Cys89Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Leber congenital amaurosis (PMID: 20702822; Invitae). ClinVar contains an entry for this variant (Variation ID: 574505). 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 AIPL1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects AIPL1 function (PMID: 23737531, 27268253, 28973376). This variant disrupts the p.Cys89 amino acid residue in AIPL1. Other variant(s) that disrupt this residue have been observed in individuals with AIPL1-related conditions (PMID: 20702822), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000696451 SCV004045921 likely pathogenic Leber congenital amaurosis 4 2022-08-24 criteria provided, single submitter clinical testing

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