ClinVar Miner

Submissions for variant NM_025114.3(CEP290):c.1936C>T (p.Gln646Ter) (rs780225183)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000313260 SCV000708162 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing
GeneDx RCV000313260 SCV000329241 pathogenic not provided 2017-06-05 criteria provided, single submitter clinical testing The Q646X variant in the CEP290 gene has been reported previously in association with Leber congenital amaurosis (Perrault et al., 2007). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q646X variant was not observed in approximately 5,600 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q646X as a disease-causing variant
Invitae RCV000636991 SCV000758439 pathogenic Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln646*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. 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 been reported as in combination with pathogenic CEP290 variants in individuals affected with Leber congenital amaurosis (PMID: 17345604) or nephronophthisis (PMID: 26673778). ClinVar contains an entry for this variant (Variation ID: 279751). Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). For these reasons, this variant has been classified as Pathogenic.

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