Submissions for variant NM_014009.4(FOXP3):c.407C>T (p.Thr136Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003625628	SCV004432916	uncertain significance	Insulin-dependent diabetes mellitus secretory diarrhea syndrome	2023-02-16	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 136 of the FOXP3 protein (p.Thr136Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FOXP3-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FOXP3 protein function. 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.
Ambry Genetics	RCV004371766	SCV004872339	uncertain significance	Inborn genetic diseases	2023-12-07	criteria provided, single submitter	clinical testing	The c.407C>T (p.T136I) alteration is located in exon 4 (coding exon 3) of the FOXP3 gene. This alteration results from a C to T substitution at nucleotide position 407, causing the threonine (T) at amino acid position 136 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.