ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1235C>T (p.Thr412Met)

gnomAD frequency: 0.00002  dbSNP: rs189280108
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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 RCV001244829 SCV001418074 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 412 of the CEP290 protein (p.Thr412Met). This variant is present in population databases (rs189280108, 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: 969468). 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 RCV002504354 SCV002814467 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2021-12-14 criteria provided, single submitter clinical testing
GeneDx RCV004720814 SCV005326902 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Natera, Inc. RCV001835216 SCV002094335 uncertain significance Leber congenital amaurosis 2020-03-03 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538514 SCV004741732 uncertain significance CEP290-related disorder 2024-06-28 no assertion criteria provided clinical testing The CEP290 c.1235C>T variant is predicted to result in the amino acid substitution p.Thr412Met. This variant has been reported in the compound heterozygous state in a patient with retinitis pigmentosa (Zhu et al. 2023. PubMed ID: 36493848). This variant is reported in 0.039% of alleles in individuals of South Asian 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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