Submissions for variant NM_007315.4(STAT1):c.865T>C (p.Tyr289His)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002651586	SCV003524887	likely pathogenic	Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency	2021-11-27	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with chronic mucocutaneous candidiasis (PMID: 27114460; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 289 of the STAT1 protein (p.Tyr289His). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Tyr289 amino acid residue in STAT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27114460, 29111217). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.