ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1105G>A (p.Glu369Lys)

gnomAD frequency: 0.00005  dbSNP: rs373414042
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001237369 SCV001410126 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 369 of the CEP290 protein (p.Glu369Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 963355). 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. 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.
Natera, Inc. RCV001834060 SCV002094340 uncertain significance Leber congenital amaurosis 2020-04-20 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538494 SCV004720075 uncertain significance CEP290-related disorder 2023-11-20 no assertion criteria provided clinical testing The CEP290 c.1105G>A variant is predicted to result in the amino acid substitution p.Glu369Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% 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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