Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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, |
RCV001701481 | SCV001929322 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001701481 | SCV001952735 | pathogenic | not provided | no assertion criteria provided | clinical testing |