ClinVar Miner

Submissions for variant NM_001079668.3(NKX2-1):c.524C>A (p.Ser175Ter)

dbSNP: rs863225300
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, University Hospital Muenster 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.