Submissions for variant NM_014009.4(FOXP3):c.409G>A (p.Ala137Thr)

dbSNP: rs1057524899

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445467	SCV000537115	uncertain significance	Monogenic diabetes	2015-11-20	criteria provided, single submitter	research	ACMG Criteria: PM2, PP3, BP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851113	SCV002120281	uncertain significance	Insulin-dependent diabetes mellitus secretory diarrhea syndrome	2022-12-03	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. 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. ClinVar contains an entry for this variant (Variation ID: 393445). This variant has not been reported in the literature in individuals affected with FOXP3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 137 of the FOXP3 protein (p.Ala137Thr).
CeGaT Center for Human Genetics Tuebingen	RCV003884541	SCV004701691	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	FOXP3: PM2:Supporting