Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002651581 | SCV003525180 | likely pathogenic | Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency | 2022-05-25 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Leu400 amino acid residue in STAT1. Other variant(s) that disrupt this residue have been observed in individuals with STAT1-related conditions (PMID: 26743090, 27114460), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects STAT1 function (PMID: 26732859). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individuals with autosomal dominant chronic mucocutaneous candidiasis (PMID: 26732859, 27114460; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 400 of the STAT1 protein (p.Leu400Val). 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. |