ClinVar Miner

Submissions for variant NM_000043.6(FAS):c.778G>A (p.Asp260Asn)

dbSNP: rs121913086
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001379330 SCV001577116 pathogenic Autoimmune lymphoproliferative syndrome type 1 2023-08-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp260 amino acid residue in FAS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9821419, 20935634). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 260 of the FAS protein (p.Asp260Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autoimmune lymphoproliferative syndrome (PMID: 18223337, 21490157; Invitae). This variant is also known as p.Asp244Asn. ClinVar contains an entry for this variant (Variation ID: 1067934). 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.
GeneDx RCV001541758 SCV001759791 pathogenic not provided 2020-09-29 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect by showing significant resistance to FAS-mediated cell death when compared with control and a reduced relative intensity in FADD and caspase-8 compared to control (Kuehn et al., 2011); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 18223337, 21490157)

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