ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1448C>T (p.Thr483Ile)

gnomAD frequency: 0.00002  dbSNP: rs373303674
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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 RCV001241474 SCV001414495 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 483 of the CEP290 protein (p.Thr483Ile). This variant is present in population databases (rs373303674, gnomAD 0.1%). 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: 966726). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002294448 SCV002587617 uncertain significance Kidney disorder 2017-05-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004609699 SCV005105320 uncertain significance Inborn genetic diseases 2024-03-26 criteria provided, single submitter clinical testing The c.1448C>T (p.T483I) alteration is located in exon 15 (coding exon 14) of the CEP290 gene. This alteration results from a C to T substitution at nucleotide position 1448, causing the threonine (T) at amino acid position 483 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001279930 SCV001467067 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538503 SCV004737303 uncertain significance CEP290-related disorder 2024-01-08 no assertion criteria provided clinical testing The CEP290 c.1448C>T variant is predicted to result in the amino acid substitution p.Thr483Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of East Asian descent in gnomAD. This variant could be benign. 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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