ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.3757C>T (p.Arg1253Cys)

gnomAD frequency: 0.00001  dbSNP: rs547677441
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002493496 SCV002784542 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2021-09-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002537855 SCV003484542 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1253 of the CEP290 protein (p.Arg1253Cys). This variant is present in population databases (rs547677441, gnomAD 0.009%). 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: 991339). 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 disruptive. 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.
Dept Of Ophthalmology, Nagoya University RCV003887986 SCV004707673 uncertain significance Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Natera, Inc. RCV001279539 SCV001466636 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004545171 SCV004759110 uncertain significance CEP290-related disorder 2024-08-06 no assertion criteria provided clinical testing The CEP290 c.3757C>T variant is predicted to result in the amino acid substitution p.Arg1253Cys. To our knowledge, this variant has not been reported in the literature. A different amino acid substitution affecting the same residue (p.Arg1253His) has been reported along with a pathogenic variant in a patient with Leber congenital amaurosis (Eisenberger et al. 2013. PubMed ID: 24265693). This variant is reported in 0.0058% of alleles in individuals of Latino 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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