Submissions for variant NM_001447.3(FAT2):c.7463C>T (p.Ala2488Val)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002993621	SCV003291716	uncertain significance	not provided	2024-01-18	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 2488 of the FAT2 protein (p.Ala2488Val). This variant is present in population databases (rs146104287, 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: 2078133). 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 with a negative predictive value of 80%. 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	RCV004065184	SCV003558404	uncertain significance	not specified	2021-10-05	criteria provided, single submitter	clinical testing	The c.7463C>T (p.A2488V) alteration is located in exon 9 (coding exon 9) of the FAT2 gene. This alteration results from a C to T substitution at nucleotide position 7463, causing the alanine (A) at amino acid position 2488 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	RCV002993621	SCV004157456	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	FAT2: BP4, BS1, BS2