Submissions for variant NM_000043.6(FAS):c.685_686del (p.Leu229fs)

dbSNP: rs2119445087

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV002275956	SCV002563026	likely pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing	FAS: PVS1:Strong, PM2, PP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV003517361	SCV004335637	pathogenic	Autoimmune lymphoproliferative syndrome type 1	2023-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu229Glufs*2) in the FAS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 107 amino acid(s) of the FAS protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1701144). This variant disrupts a region of the FAS protein in which other variant(s) (p.Leu294*) have been determined to be pathogenic (PMID: 10090885, 21490157, 23407489). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.