ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4837C>G (p.Pro1613Ala)

gnomAD frequency: 0.00003  dbSNP: rs769280708
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000636998 SCV000758446 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1613 of the CEP290 protein (p.Pro1613Ala). This variant is present in population databases (rs769280708, gnomAD 0.008%). 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: 530920). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002507079 SCV002816292 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004533333 SCV004121191 uncertain significance CEP290-related disorder 2023-05-24 criteria provided, single submitter clinical testing The CEP290 c.4837C>G variant is predicted to result in the amino acid substitution p.Pro1613Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0078% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88476983-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004025486 SCV004926235 uncertain significance Inborn genetic diseases 2024-02-26 criteria provided, single submitter clinical testing The c.4837C>G (p.P1613A) alteration is located in exon 37 (coding exon 36) of the CEP290 gene. This alteration results from a C to G substitution at nucleotide position 4837, causing the proline (P) at amino acid position 1613 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001835026 SCV002094204 uncertain significance Leber congenital amaurosis 2019-10-28 no assertion criteria provided clinical testing

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