ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4741C>T (p.Leu1581Phe)

gnomAD frequency: 0.00011  dbSNP: rs11831931
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193603 SCV000246995 uncertain significance not specified 2015-04-14 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073469 SCV001239012 uncertain significance Retinal dystrophy 2019-03-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001366563 SCV001562870 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1581 of the CEP290 protein (p.Leu1581Phe). This variant is present in population databases (rs11831931, gnomAD 0.01%). 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: 210696). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV002517924 SCV003740569 uncertain significance Inborn genetic diseases 2021-06-18 criteria provided, single submitter clinical testing The c.4741C>T (p.L1581F) alteration is located in exon 36 (coding exon 35) of the CEP290 gene. This alteration results from a C to T substitution at nucleotide position 4741, causing the leucine (L) at amino acid position 1581 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005008125 SCV005630035 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2024-06-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828016 SCV002094209 uncertain significance Leber congenital amaurosis 2019-10-28 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004530108 SCV004110244 uncertain significance CEP290-related disorder 2024-08-19 no assertion criteria provided clinical testing The CEP290 c.4741C>T variant is predicted to result in the amino acid substitution p.Leu1581Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% 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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