ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.5145T>G (p.Asn1715Lys)

dbSNP: rs568619750
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480766 SCV000571822 uncertain significance not provided 2018-12-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CEP290 gene. The N1715K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N1715K variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project and was not observed with any significant frequency in the 1000 Genomes Project. The N1715K 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 across species, and in silico analysis predicts this variant is probably 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001247847 SCV001421298 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1715 of the CEP290 protein (p.Asn1715Lys). This variant is present in population databases (rs568619750, 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: 422365). 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 expected to disrupt CEP290 protein function with a positive predictive value of 80%. 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 RCV002481521 SCV002775566 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2021-09-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV001273061 SCV001455648 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing

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