ClinVar Miner

Submissions for variant NM_025114.3(CEP290):c.3660G>T (p.Lys1220Asn) (rs201982308)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724196 SCV000229464 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763865 SCV000894799 uncertain significance Leber congenital amaurosis 10; Meckel syndrome type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000724196 SCV000564861 uncertain significance not provided 2017-05-31 criteria provided, single submitter clinical testing A variant of unknown significance has been identified in the CEP290 gene. The K1220N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes Project. The K1220N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000797414 SCV000936969 uncertain significance Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1220 of the CEP290 protein (p.Lys1220Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs201982308, ExAC 0.05%). This variant has not been reported in the literature in individuals with CEP290-related disease. ClinVar contains an entry for this variant (Variation ID: 196713). 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 C35"). 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.

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