ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2594_2595del (p.Leu865fs) (rs1221464366)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008546 SCV001168319 likely pathogenic not provided 2019-01-25 criteria provided, single submitter clinical testing The c.2594_2595delTC variant in the CEP290 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2594_2595delTC variant causes a frameshift starting with codon Leucine 865, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Leu865GlnfsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2594_2595delTC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.2594_2595delTC as a likely pathogenic variant.
Baylor Genetics RCV001330037 SCV001521628 likely pathogenic Joubert syndrome 5 2019-03-02 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001384273 SCV001583707 pathogenic Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2020-05-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu865Glnfs*9) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 817418). Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115, 25377065, 28559085). For these reasons, this variant has been classified as Pathogenic.

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