ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.3911T>C (p.Met1304Thr)

gnomAD frequency: 0.00001  dbSNP: rs761010723
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988883 SCV001138781 uncertain significance Joubert syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001296623 SCV001485594 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1304 of the CEP290 protein (p.Met1304Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with inherited retinal dystrophy (PMID: 32865313; Invitae). ClinVar contains an entry for this variant (Variation ID: 802877). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV003324545 SCV004030367 uncertain significance Retinitis pigmentosa 2023-07-24 criteria provided, single submitter research Clinical significance based on ACMG v2.0
Natera, Inc. RCV001827131 SCV002094242 uncertain significance Leber congenital amaurosis 2020-04-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733103 SCV005363142 uncertain significance CEP290-related disorder 2024-08-12 no assertion criteria provided clinical testing The CEP290 c.3911T>C variant is predicted to result in the amino acid substitution p.Met1304Thr. This variant has been reported in individuals with inherited retinal dystrophies (compound heterozygous, Supplementary Table S2, Peter et al. 2023. PubMed ID: 36909829; Sallum et al. 2020. PubMed ID: 32865313). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. 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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