ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.3787C>A (p.Leu1263Met)

gnomAD frequency: 0.00022  dbSNP: rs370395204
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000636986 SCV000758434 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1263 of the CEP290 protein (p.Leu1263Met). This variant is present in population databases (rs370395204, gnomAD 0.03%). 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: 530913). 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 CEP290 protein function with a positive predictive value of 80%. 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.
Eurofins Ntd Llc (ga) RCV000733946 SCV000862052 uncertain significance not provided 2018-07-03 criteria provided, single submitter clinical testing
GeneDx RCV000733946 SCV001998398 uncertain significance not provided 2019-11-21 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001273077 SCV001455664 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004533332 SCV004727540 uncertain significance CEP290-related disorder 2024-08-21 no assertion criteria provided clinical testing The CEP290 c.3787C>A variant is predicted to result in the amino acid substitution p.Leu1263Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.037% 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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