ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.676G>A (p.Val226Ile)

gnomAD frequency: 0.00007  dbSNP: rs750099371
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001248290 SCV001421763 uncertain significance Leber congenital amaurosis 2; Retinitis pigmentosa 20 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 226 of the RPE65 protein (p.Val226Ile). This variant is present in population databases (rs750099371, gnomAD 0.006%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 28224992). ClinVar contains an entry for this variant (Variation ID: 972295). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. RCV001830037 SCV002092764 uncertain significance Leber congenital amaurosis 2020-07-10 no assertion criteria provided clinical testing

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