ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4978T>A (p.Leu1660Ile)

gnomAD frequency: 0.00012  dbSNP: rs372557655
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637001 SCV000758449 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1660 of the CEP290 protein (p.Leu1660Ile). This variant is present in population databases (rs372557655, gnomAD 0.04%). 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: 530922). 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 not expected to disrupt CEP290 protein function with a negative 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.
Eurofins Ntd Llc (ga) RCV000733950 SCV000862056 uncertain significance not provided 2018-07-03 criteria provided, single submitter clinical testing
GeneDx RCV000733950 SCV001998400 uncertain significance not provided 2019-11-21 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002528888 SCV003693193 uncertain significance Inborn genetic diseases 2022-10-03 criteria provided, single submitter clinical testing The c.4978T>A (p.L1660I) alteration is located in exon 37 (coding exon 36) of the CEP290 gene. This alteration results from a T to A substitution at nucleotide position 4978, causing the leucine (L) at amino acid position 1660 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001273064 SCV001455651 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004533335 SCV004723512 uncertain significance CEP290-related disorder 2024-08-21 no assertion criteria provided clinical testing The CEP290 c.4978T>A variant is predicted to result in the amino acid substitution p.Leu1660Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.049% 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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