ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.726T>A (p.Asn242Lys)

gnomAD frequency: 0.00001  dbSNP: rs949161264
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001822440 SCV002066873 uncertain significance not specified 2021-02-12 criteria provided, single submitter clinical testing This sequence change does not appear to have been previously described in patients with CEP290-related disorders and has also not been described in the large population databases such as ExAC and gnomAD (dbSNP rs949161264). The p.Asn242Lys change affects a moderately conserved amino acid residue located in a domain of the CEP290 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asn242Lys substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Asn242Lys change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869755 SCV002285575 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 242 of the CEP290 protein (p.Asn242Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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 RCV005006078 SCV005632028 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2024-01-09 criteria provided, single submitter clinical testing

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