Submissions for variant NM_000043.6(FAS):c.749G>C (p.Arg250Pro)

dbSNP: rs121913080

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000638906	SCV000760460	pathogenic	Autoimmune lymphoproliferative syndrome type 1	2023-07-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 250 of the FAS protein (p.Arg250Pro). For these reasons, this variant has been classified as Pathogenic. 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: 10090885, 18948840, 21490157). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects FAS function (PMID: 9927496, 10090885, 21490157). 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. ClinVar contains an entry for this variant (Variation ID: 16505). This variant is also known as c.943G>C (p.R234P). This variant has been observed in individual(s) with autoimmue lymphoproliferative syndrome (PMID: 10090885). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
OMIM	RCV000017969	SCV000038248	pathogenic	Autoimmune lymphoproliferative syndrome, type 1a	1999-02-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701481	SCV001929322	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001701481	SCV001952735	pathogenic	not provided		no assertion criteria provided	clinical testing