ClinVar Miner

Submissions for variant NM_004208.4(AIFM1):c.1265G>A (p.Arg422Gln)

dbSNP: rs724160021
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne 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, Xijing Hospital 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

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