Submissions for variant NM_001447.3(FAT2):c.10148C>T (p.Ala3383Val)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002943356	SCV003275204	uncertain significance	not provided	2023-09-08	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3383 of the FAT2 protein (p.Ala3383Val). This variant is present in population databases (rs150088361, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FAT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2064288). 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 FAT2 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	RCV004068011	SCV003758377	uncertain significance	not specified	2022-04-08	criteria provided, single submitter	clinical testing	The c.10148C>T (p.A3383V) alteration is located in exon 15 (coding exon 15) of the FAT2 gene. This alteration results from a C to T substitution at nucleotide position 10148, causing the alanine (A) at amino acid position 3383 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV002943356	SCV004157444	benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	FAT2: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003943631	SCV004762810	likely benign	FAT2-related disorder	2022-06-23	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).