Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760480 | SCV000890369 | pathogenic | not provided | 2022-10-20 | criteria provided, single submitter | clinical testing | Reported in unrelated patients with benign hereditary chorea referred for genetic testing at GeneDx and in the published literature (Ferrara et al., 2008; Salvatore et al., 2010); Nonsense variant predicted to result in protein truncation, as the last 227 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Published functional studies demonstrate p.(S175*) renders the NKX2-1 protein unable to translocate into the nucleus (Ferrara et al., 2008); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24555207, 20544814, 18788921, 27066577) |
Institute of Human Genetics, |
RCV002287392 | SCV002577883 | pathogenic | Dystonic disorder | 2021-12-20 | criteria provided, single submitter | clinical testing | ACMG categories: PVS1,PM2,PP5 |
Invitae | RCV000760480 | SCV003442330 | pathogenic | not provided | 2021-12-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser175*) in the NKX2-1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 227 amino acid(s) of the NKX2-1 protein. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects NKX2-1 function (PMID: 18788921). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 217884). This variant is also known as c.609C>A (p.S145X). This premature translational stop signal has been observed in individual(s) with NKX2-1 related conditions (PMID: 18788921, 27066577). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). |
Mendelics | RCV000201946 | SCV000256880 | pathogenic | Brain-lung-thyroid syndrome | 2014-08-01 | no assertion criteria provided | clinical testing |