ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4121A>G (p.Tyr1374Cys)

gnomAD frequency: 0.00003  dbSNP: rs1337676817
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001201724 SCV001372810 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1374 of the CEP290 protein (p.Tyr1374Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. 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 disruptive. 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 RCV002484077 SCV002788881 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-03-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828621 SCV002094234 uncertain significance Leber congenital amaurosis 2021-03-09 no assertion criteria provided clinical testing

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