ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2273T>C (p.Val758Ala)

gnomAD frequency: 0.00002  dbSNP: rs369868981
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001313881 SCV001504391 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 758 of the CEP290 protein (p.Val758Ala). This variant is present in population databases (rs369868981, gnomAD 0.006%). 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: 1015064). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV002476452 SCV002789105 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-05-14 criteria provided, single submitter clinical testing
GeneDx RCV001700733 SCV005080137 uncertain significance not provided 2023-07-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Clinical Genetics, Academic Medical Center RCV001700733 SCV001926232 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001700733 SCV001968382 uncertain significance not provided no assertion criteria provided clinical testing
Natera, Inc. RCV001835549 SCV002094295 uncertain significance Leber congenital amaurosis 2020-04-21 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733245 SCV005349005 uncertain significance CEP290-related disorder 2024-04-10 no assertion criteria provided clinical testing The CEP290 c.2273T>C variant is predicted to result in the amino acid substitution p.Val758Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0076% of alleles in individuals of European (Non-Finnish) 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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