Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001214333 | SCV001386010 | uncertain significance | Insulin-dependent diabetes mellitus secretory diarrhea syndrome | 2023-07-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome (PMID: 30443250). ClinVar contains an entry for this variant (Variation ID: 944023). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 323 of the FOXP3 protein (p.Glu323Lys). This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. |