ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.5777G>C (p.Arg1926Pro)

dbSNP: rs778030031
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815985 SCV000956469 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2025-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1926 of the CEP290 protein (p.Arg1926Pro). This variant is present in population databases (rs778030031, gnomAD 0.0009%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 21153841, 29398085, 31630094, 32865313). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 659046). 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%. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000988881 SCV001138779 likely pathogenic Joubert syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002495153 SCV002792433 likely pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2024-06-13 criteria provided, single submitter clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV003324535 SCV004030369 likely pathogenic Retinitis pigmentosa 2023-07-24 criteria provided, single submitter research Clinical significance based on ACMG v2.0
Baylor Genetics RCV003467476 SCV004216542 pathogenic Bardet-Biedl syndrome 14 2023-12-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004733054 SCV005356951 likely pathogenic CEP290-related disorder 2024-07-06 no assertion criteria provided clinical testing The CEP290 c.5777G>C variant is predicted to result in the amino acid substitution p.Arg1926Pro. This variant was reported in individuals with Leber congenital amaurosis/ retinal dystrophy (Table 2, Wiszniewski et al 2011. PubMed ID: 21153841; Table 1, Sheck et al 2018. PubMed ID: 29398085; Table S1, Xu et al 2019. PubMed ID: 31630094; Sallum  et al 2020. PubMed ID: 32865313). This variant is reported in 0.00092% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic.

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