Submissions for variant NM_000043.6(FAS):c.536T>G (p.Leu179Arg)

dbSNP: rs1554851718

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626571	SCV000747272	likely pathogenic	Splenomegaly	2017-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV001051234	SCV001215378	likely pathogenic	Autoimmune lymphoproliferative syndrome type 1	2022-01-19	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 523313). This missense change has been observed in individual(s) with autoimmune lymphoproliferative syndrome (ALPS) (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 179 of the FAS protein (p.Leu179Arg).
CeGaT Center for Human Genetics Tuebingen	RCV001815421	SCV002062932	uncertain significance	not provided	2021-10-01	criteria provided, single submitter	clinical testing