Submissions for variant NM_000043.6(FAS):c.580G>A (p.Glu194Lys)

gnomAD frequency: 0.00138  dbSNP: rs56006128

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766928	SCV000321627	uncertain significance	not provided	2024-12-31	criteria provided, single submitter	clinical testing	Reported previously in association with autoimmune lymphoproliferative syndrome type 1A (PMID: 16537120, 19214977, 32441320, 33838017, 36844186); Functional studies have shown that E194K decreases the function of the FAS protein (PMID: 24043286); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27153395, 27884173, 24728327, 19214977, 31172514, 31939527, 36268024, 32441320, 33838017, 36844186, 35741048, 16537120, 24043286)
Illumina Laboratory Services, Illumina	RCV000407819	SCV000365904	likely benign	Autoimmune lymphoproliferative syndrome type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000407819	SCV000637309	likely benign	Autoimmune lymphoproliferative syndrome type 1	2025-02-03	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000407819	SCV000898684	uncertain significance	Autoimmune lymphoproliferative syndrome type 1	2021-03-30	criteria provided, single submitter	clinical testing	FAS NM_000043.5 exon7 p.Glu194Lys (c.580G>A): This variant has been reported in the literature in at least one individual with autoimmune lymphoproliferative syndrome (ALPS)(Campagnoli 2006 PMID:16537120, Boggio 2013 PMID:24043286). This variant is present in 0.2% (306/126586) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/dbsnp/rs56006128). This variant is present in ClinVar (Variation ID:134374). Evolutionary conservation and computational predictive tools for this variant are unclear. In vitro functional studies suggest that this variant will impact the protein (Boggio 2013 PMID:24043286). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Baylor Genetics	RCV000407819	SCV001524336	uncertain significance	Autoimmune lymphoproliferative syndrome type 1	2019-09-06	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genetic Services Laboratory, University of Chicago	RCV000121048	SCV002070461	uncertain significance	not specified	2017-08-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000407819	SCV003833948	uncertain significance	Autoimmune lymphoproliferative syndrome type 1	2021-02-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766928	SCV004127055	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	FAS: BP4, BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000121048	SCV005076631	likely benign	not specified	2024-04-23	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000766928	SCV005412175	uncertain significance	not provided	2024-05-15	criteria provided, single submitter	clinical testing	BS1, BS2, PS4_moderate
ITMI	RCV000121048	SCV000085216	not provided	not specified	2013-09-19	no assertion provided	reference population
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000766928	SCV001807749	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000766928	SCV001928091	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000766928	SCV001970375	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935155	SCV004752775	likely benign	FAS-related disorder	2020-06-26	no assertion criteria provided	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).