Submissions for variant NM_001079668.3(NKX2-1):c.626G>C (p.Arg209Pro)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV002463841	SCV002758027	pathogenic	Hereditary ataxia; Chorea	2022-12-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV002466760	SCV002762679	likely pathogenic	Brain-lung-thyroid syndrome	2022-05-24	criteria provided, single submitter	clinical testing	The NKX2-1 c.626G>C (p.Arg209Pro) missense variant results in the substitution of arginine at amino acid position 209 with proline. This variant has been reported in a total of two unrelated families with choreoathetosis, hypothyroidism, and neonatal respiratory distress (also referred to brain-thyroid-lung syndrome) in a heterozygous state (Williamson et al. 2014; Guaquelin et al. 2017). In one family the variant was present in two brothers with the condition as well as in the affected daughter of one of the brothers (Williamson et al. 2014). This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Multiple lines of computational evidence suggest the variant may have a deleterious effect on the gene or gene product. Based on the available evidence, the c.626G>C (p.Arg209Pro) variant is classified as likely pathogenic for choreoathetosis, hypothyroidism, and neonatal respiratory distress.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV002466760	SCV003935961	likely pathogenic	Brain-lung-thyroid syndrome	2020-02-28	criteria provided, single submitter	clinical testing