ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.7341_7344dup (p.Ser2449fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kariminejad - Najmabadi Pathology & Genetics Center RCV001030765 SCV001194260 likely pathogenic Rod-cone dystrophy 2017-09-03 criteria provided, single submitter clinical testing
Invitae RCV001231786 SCV001404318 pathogenic Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2019-11-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CEP290 gene (p.Ser2449Thrfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acids of the CEP290 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CEP290-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the CEP290 protein. Other variant(s) that disrupt this region (p.Thr2457Alafs*27) have been determined to be pathogenic (PMID: 30193310). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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