Submissions for variant NM_000306.4(POU1F1):c.649C>T (p.Arg217Ter)

gnomAD frequency: 0.00001  dbSNP: rs761275346

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pediatrics, Taipei Veterans General Hospital	RCV001293685	SCV001759936	pathogenic	Pituitary hormone deficiency, combined, 1	2020-12-09	criteria provided, single submitter	clinical testing
Invitae	RCV003546697	SCV004267111	pathogenic	not provided	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg217*) in the POU1F1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 75 amino acid(s) of the POU1F1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of POU1F1-related conditions (PMID: 34815942). ClinVar contains an entry for this variant (Variation ID: 998004). This variant disrupts a region of the POU1F1 protein in which other variant(s) (p.Glu250Asnfs*2) have been determined to be pathogenic (PMID: 11297581). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital	RCV001293685	SCV001482407	likely pathogenic	Pituitary hormone deficiency, combined, 1	2019-05-31	no assertion criteria provided	research