ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4156A>G (p.Ile1386Val)

gnomAD frequency: 0.00002  dbSNP: rs1427374639
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001813032 SCV001473276 uncertain significance not provided 2019-09-19 criteria provided, single submitter clinical testing The CEP290 c.4156A>G; p.Ile1386Val variant (rs1427374639), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The isoleucine at codon 1386 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of this variant cannot be determined with certainty.
Labcorp Genetics (formerly Invitae), Labcorp RCV002541776 SCV003512782 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-01-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1386 of the CEP290 protein (p.Ile1386Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 994031). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002537947 SCV003538231 uncertain significance Inborn genetic diseases 2021-10-26 criteria provided, single submitter clinical testing The c.4156A>G (p.I1386V) alteration is located in exon 32 (coding exon 31) of the CEP290 gene. This alteration results from a A to G substitution at nucleotide position 4156, causing the isoleucine (I) at amino acid position 1386 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001836254 SCV002094232 uncertain significance Leber congenital amaurosis 2021-07-20 no assertion criteria provided clinical testing

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