ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.6572A>T (p.His2191Leu)

gnomAD frequency: 0.00011  dbSNP: rs368428115
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001233247 SCV001405831 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 2191 of the CEP290 protein (p.His2191Leu). This variant is present in population databases (rs368428115, 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: 959829). 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 RCV002484276 SCV002791049 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-02-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003963141 SCV004784238 uncertain significance CEP290-related condition 2023-11-11 criteria provided, single submitter clinical testing The CEP290 c.6572A>T variant is predicted to result in the amino acid substitution p.His2191Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88453748-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001834023 SCV002091837 uncertain significance Leber congenital amaurosis 2020-01-17 no assertion criteria provided clinical testing

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