Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV000787039 | SCV000925954 | likely pathogenic | Brain-lung-thyroid syndrome | 2019-03-25 | criteria provided, single submitter | clinical testing | This frameshift variant is predicted to lead to a new stop codon that is downstream of the native stop codon. The resulting transcript is not expected to undergo nonsense-mediated decay and likely results in an extended protein product (125 novel C-terminal amino acids replacing the last 89 amino acids of NKX2-1). The glutamine rich region, predicted to be missing from the resulting protein, has an important role in NKX2-1 transactivation. This NKX2-1 variant is absent* from large population datasets and has not been reported in ClinVar nor the literature, to our knowledge. This variant is considered likely pathogenic. |