Submissions for variant NM_000043.6(FAS):c.749G>A (p.Arg250Gln)

dbSNP: rs121913080

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001382235	SCV001580910	pathogenic	Autoimmune lymphoproliferative syndrome type 1	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 250 of the FAS protein (p.Arg250Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autoimmune lymphoproliferative syndrome (PMID: 10090885, 11830507, 18948840). This variant is also known as R234Q. ClinVar contains an entry for this variant (Variation ID: 1070182). 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 expected to disrupt FAS protein function. Experimental studies have shown that this missense change affects FAS function (PMID: 18948840, 21490157). This variant disrupts the p.Arg250 amino acid residue in FAS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9927496, 10090885). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001702895	SCV002821533	likely pathogenic	not provided	2024-05-01	criteria provided, single submitter	clinical testing	FAS: PM1, PM2, PM5, PS4:Moderate, PS3:Supporting
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001702895	SCV005197859	pathogenic	not provided	2022-10-18	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702895	SCV001929791	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001702895	SCV001955311	pathogenic	not provided		no assertion criteria provided	clinical testing