Submissions for variant NM_001447.3(FAT2):c.5512T>C (p.Phe1838Leu)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004202613	SCV003705721	uncertain significance	not specified	2022-08-22	criteria provided, single submitter	clinical testing	The c.5512T>C (p.F1838L) alteration is located in exon 9 (coding exon 9) of the FAT2 gene. This alteration results from a T to C substitution at nucleotide position 5512, causing the phenylalanine (F) at amino acid position 1838 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Invitae	RCV003575016	SCV004365420	uncertain significance	not provided	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1838 of the FAT2 protein (p.Phe1838Leu). This variant is present in population databases (rs142666998, 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: 2367138). 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. 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.
PreventionGenetics, part of Exact Sciences	RCV003946395	SCV004762957	likely benign	FAT2-related disorder	2022-05-31	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).