ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.998A>C (p.Asn333Thr)

gnomAD frequency: 0.00005  dbSNP: rs376033047
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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 RCV001060727 SCV001225433 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-06-29 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 333 of the CEP290 protein (p.Asn333Thr). This variant is present in population databases (rs376033047, gnomAD 0.004%). 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: 855452). 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.
GeneDx RCV002553888 SCV003195187 uncertain significance not provided 2022-07-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004609604 SCV005105324 uncertain significance Inborn genetic diseases 2024-05-28 criteria provided, single submitter clinical testing The c.998A>C (p.N333T) alteration is located in exon 12 (coding exon 11) of the CEP290 gene. This alteration results from a A to C substitution at nucleotide position 998, causing the asparagine (N) at amino acid position 333 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001274131 SCV001457928 uncertain significance Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing

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