ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1626T>G (p.Ile542Met)

gnomAD frequency: 0.00001  dbSNP: rs762272190
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001296843 SCV001485818 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 542 of the CEP290 protein (p.Ile542Met). This variant is present in population databases (rs762272190, gnomAD 0.007%). 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: 1000685). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV004036050 SCV004926215 uncertain significance Inborn genetic diseases 2022-09-29 criteria provided, single submitter clinical testing The c.1626T>G (p.I542M) alteration is located in exon 17 (coding exon 16) of the CEP290 gene. This alteration results from a T to G substitution at nucleotide position 1626, causing the isoleucine (I) at amino acid position 542 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001835403 SCV002094324 uncertain significance Leber congenital amaurosis 2020-06-01 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004531079 SCV004741805 uncertain significance CEP290-related disorder 2024-06-30 no assertion criteria provided clinical testing The CEP290 c.1626T>G variant is predicted to result in the amino acid substitution p.Ile542Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0069% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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