ClinVar Miner

Submissions for variant NM_007315.4(STAT1):c.1256C>G (p.Thr419Arg)

dbSNP: rs1347113886
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000805201 SCV000945148 uncertain significance Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency 2022-08-09 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects STAT1 function (PMID: 32582194, 33679782). 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"). ClinVar contains an entry for this variant (Variation ID: 650110). This missense change has been observed in individual(s) with chronic mucocutaneous candidiasis (PMID: 27114460). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 419 of the STAT1 protein (p.Thr419Arg).
Illumina Laboratory Services, Illumina RCV001270751 SCV001451500 uncertain significance Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome 2019-02-21 criteria provided, single submitter clinical testing The STAT1 c.1256C>G (p.Thr419Arg) variant is a missense variant that has been reported in one study and identified in two related individuals in a heterozygous state (Toubiana et al. 2016). The two individuals have a clinical diagnosis of chronic mucocutaneous candidiasis (CMC). Control data are unavailable for this variant and it has not been reported in the Genome Aggregation Database in a region of good sequence coverage so the variant is presumed to be rare. The variant is located in the DNA-binding domain of the STAT1 protein; other variants in the domain have been found in individuals with CMC. Based on the limited evidence, the p.Thr419Arg variant is classified as a variant of uncertain significance for chronic mucocutaneous candidiasis disease.

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