Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Equipe Genetique des Anomalies du Developpement, |
RCV000149865 | SCV003920981 | pathogenic | Deafness, X-linked 5 | 2023-01-25 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003467209 | SCV004192949 | likely pathogenic | Severe X-linked mitochondrial encephalomyopathy | 2023-01-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003764900 | SCV004571544 | pathogenic | Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency | 2023-07-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg422 amino acid residue in AIFM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25986071, 31850270). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 AIFM1 protein function. ClinVar contains an entry for this variant (Variation ID: 162480). This missense change has been observed in individual(s) with clinical features of AIFM1-related conditions (PMID: 25986071). It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 422 of the AIFM1 protein (p.Arg422Gln). |
Deafness Gene Diagnosis, |
RCV000149865 | SCV000196719 | likely pathogenic | Deafness, X-linked 5 | no assertion criteria provided | clinical testing | ||
OMIM | RCV000149865 | SCV000257356 | pathogenic | Deafness, X-linked 5 | 2015-08-01 | no assertion criteria provided | literature only |