ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.974T>C (p.Ile325Thr)

gnomAD frequency: 0.00008  dbSNP: rs769705837
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691545 SCV000819330 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 325 of the CEP290 protein (p.Ile325Thr). This variant is present in population databases (rs769705837, gnomAD 0.01%). 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: 570641). 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. 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.
Fulgent Genetics, Fulgent Genetics RCV002477559 SCV002788123 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-17 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV003424284 SCV004116739 uncertain significance CEP290-related condition 2023-05-31 criteria provided, single submitter clinical testing The CEP290 c.974T>C variant is predicted to result in the amino acid substitution p.Ile325Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88520184-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001275041 SCV001459795 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing

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