ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.13A>T (p.Ile5Leu)

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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 RCV002588971 SCV002948548 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-02-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 5 of the CEP290 protein (p.Ile5Leu). This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 1906149). 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 with a negative predictive value of 80%. This variant disrupts the p.Ile5 amino acid residue in CEP290. Other variant(s) that disrupt this residue have been observed in individuals with CEP290-related conditions (PMID: 32865313, 33946315), which suggests that this may be a clinically significant amino acid residue. 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 RCV004733516 SCV005353250 uncertain significance CEP290-related disorder 2024-03-05 no assertion criteria provided clinical testing The CEP290 c.13A>T variant is predicted to result in the amino acid substitution p.Ile5Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0083% of alleles in individuals of African 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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