ClinVar Miner

Submissions for variant NM_001077350.3(NPRL3):c.1270C>T (p.Arg424Ter)

gnomAD frequency: 0.00001  dbSNP: rs886037961
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000241508 SCV001213929 pathogenic Epilepsy, familial focal, with variable foci 3 2023-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg424*) in the NPRL3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPRL3 are known to be pathogenic (PMID: 26285051, 26505888). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with focal epilepsy (PMID: 27173016). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 254360). For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000241508 SCV001994779 pathogenic Epilepsy, familial focal, with variable foci 3 2021-10-18 criteria provided, single submitter clinical testing
GeneDx RCV002281079 SCV002569770 pathogenic not provided 2023-05-08 criteria provided, single submitter clinical testing Reported previously in an individual with refractory focal epilepsy (Abumurad et al., 221); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34868250, 34693554, 33461085, 33741238, 30093711, 27173016, 30485578, 36864519, 37099548, 34235417, 36937533)
OMIM RCV000241508 SCV000299385 pathogenic Epilepsy, familial focal, with variable foci 3 2016-09-21 no assertion criteria provided literature only

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