ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1517G>A (p.Arg506His)

gnomAD frequency: 0.00001  dbSNP: rs866571949
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502930 SCV000594069 uncertain significance not specified 2017-06-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001306711 SCV001496092 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 506 of the CEP290 protein (p.Arg506His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 434742). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
GeneDx RCV001764483 SCV001989467 uncertain significance not provided 2019-11-12 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004609410 SCV005105323 uncertain significance Inborn genetic diseases 2024-05-24 criteria provided, single submitter clinical testing The c.1517G>A (p.R506H) alteration is located in exon 15 (coding exon 14) of the CEP290 gene. This alteration results from a G to A substitution at nucleotide position 1517, causing the arginine (R) at amino acid position 506 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005010427 SCV005631992 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2024-03-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV001279928 SCV001467065 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing

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