Submissions for variant NM_001291303.3(FAT4):c.8078C>T (p.Ser2693Leu)

gnomAD frequency: 0.00025  dbSNP: rs148918820

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766651	SCV000581920	uncertain significance	not provided	2023-03-21	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago	RCV000493812	SCV000594748	uncertain significance	not specified	2016-12-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000766651	SCV001566704	uncertain significance	not provided	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2691 of the FAT4 protein (p.Ser2691Leu). This variant is present in population databases (rs148918820, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. ClinVar contains an entry for this variant (Variation ID: 429367). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FAT4 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.
Fulgent Genetics, Fulgent Genetics	RCV005034031	SCV005659962	uncertain significance	Van Maldergem syndrome 2; Hennekam lymphangiectasia-lymphedema syndrome 2	2024-02-08	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000766651	SCV001957702	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000766651	SCV001966247	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751566	SCV005361140	uncertain significance	FAT4-related disorder	2024-05-15	no assertion criteria provided	clinical testing	The FAT4 c.8078C>T variant is predicted to result in the amino acid substitution p.Ser2693Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.