ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1664A>T (p.Lys555Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002585479 SCV003493732 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 555 of the CEP290 protein (p.Lys555Ile). This variant is present in population databases (rs369231584, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of leber congenital amaurosis (PMID: 34196655). 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 not 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.
PreventionGenetics, part of Exact Sciences RCV004733586 SCV005350245 uncertain significance CEP290-related disorder 2024-09-25 no assertion criteria provided clinical testing The CEP290 c.1664A>T variant is predicted to result in the amino acid substitution p.Lys555Ile. This variant has been reported along with a second CEP290 variant in two patients with retinitis pigmentosa (Karali et al. 2020. PubMed ID: 31877679; Testa et al. 2021. PubMed ID: 34196655). This variant is reported in 0.0086% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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