ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.3778G>A (p.Ala1260Thr)

gnomAD frequency: 0.00007  dbSNP: rs375609644
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001058859 SCV001223455 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1260 of the CEP290 protein (p.Ala1260Thr). This variant is present in population databases (rs375609644, 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: 853936). 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 not expected to disrupt CEP290 protein function with a negative 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.
Fulgent Genetics, Fulgent Genetics RCV002479356 SCV002784136 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2021-08-22 criteria provided, single submitter clinical testing
Natera, Inc. RCV001827374 SCV002094249 uncertain significance Leber congenital amaurosis 2021-05-19 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733136 SCV005344593 uncertain significance CEP290-related disorder 2024-04-22 no assertion criteria provided clinical testing The CEP290 c.3778G>A variant is predicted to result in the amino acid substitution p.Ala1260Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.029% 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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