ClinVar Miner

Submissions for variant NM_022787.4(NMNAT1):c.507G>A (p.Trp169Ter) (rs371526758)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255071 SCV000322384 pathogenic not provided 2017-03-15 criteria provided, single submitter clinical testing The W169X pathogenic variant in the NMNAT1 gene has been reported previously either in the homozygous state or in combination with another NMNAT1 variant in multiple unrelated individuals with Leber congenital amaurosis (Chiang et al., 2012; Koenekoop et al., 2012; Perrault et al., 2012). This variant is predicted to cause loss of normal protein function through protein truncation. The W169X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret W169X as a pathogenic variant.
Invitae RCV000030768 SCV001407778 pathogenic Leber congenital amaurosis 9 2019-09-20 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NMNAT1 gene (p.Trp169*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 111 amino acids of the NMNAT1 protein. This variant is present in population databases (rs371526758, ExAC 0.003%). This variant has been observed in individual(s) with Leber congenital amaurosis (PMID:22842231, 29178642, 22842229, 22842230). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 265453). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000030768 SCV000053429 pathogenic Leber congenital amaurosis 9 2012-09-01 no assertion criteria provided literature only

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