ClinVar Miner

Submissions for variant NM_001079668.3(NKX2-1):c.872C>T (p.Pro291Leu)

dbSNP: rs1057519223
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000415944 SCV000493634 likely pathogenic not provided 2017-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000415944 SCV002504265 pathogenic not provided 2022-04-21 criteria provided, single submitter clinical testing Identified in a patient with chorea, hypotonia, and neonatal respiratory distress in published literature (Peall et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24171694)
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV003236798 SCV003935945 likely pathogenic Brain-lung-thyroid syndrome 2020-01-24 criteria provided, single submitter clinical testing
Invitae RCV000415944 SCV004296334 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 291 of the NKX2-1 protein (p.Pro291Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with NKX2-1-related conditions (PMID: 24171694). ClinVar contains an entry for this variant (Variation ID: 374740). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Pro291 amino acid residue in NKX2-1. Other variant(s) that disrupt this residue have been observed in individuals with NKX2-1-related conditions (PMID: 30352709), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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