ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1742A>C (p.Glu581Ala)

gnomAD frequency: 0.00025  dbSNP: rs77579747
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001314251 SCV001504776 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-07-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 581 of the CEP290 protein (p.Glu581Ala). This variant is present in population databases (rs77579747, gnomAD 0.07%). 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: 1015401). 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 tolerated. 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 RCV002476455 SCV002779861 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-01-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004531103 SCV004115062 uncertain significance CEP290-related disorder 2024-01-05 criteria provided, single submitter clinical testing The CEP290 c.1742A>C variant is predicted to result in the amino acid substitution p.Glu581Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.078% of alleles in individuals of African descent in gnomAD, which may be too common to be an undocumented disease causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001835551 SCV002094321 uncertain significance Leber congenital amaurosis 2020-02-04 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.