Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000415225 | SCV000492840 | likely pathogenic | Sensorineural hearing loss disorder; Pes planus; Distal muscle weakness; Foot dorsiflexor weakness | 2015-08-06 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001311404 | SCV001501562 | pathogenic | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001385157 | SCV001584918 | pathogenic | Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency | 2021-06-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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 AIFM1 protein function. This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 25590979, 31523922, 28967629). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 374094). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 340 of the AIFM1 protein (p.Met340Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. |
Inherited Neuropathy Consortium | RCV000789722 | SCV000929099 | uncertain significance | Charcot-Marie-Tooth disease X-linked recessive 4 | no assertion criteria provided | literature only | ||
OMIM | RCV000789722 | SCV001052585 | pathogenic | Charcot-Marie-Tooth disease X-linked recessive 4 | 2019-12-10 | no assertion criteria provided | literature only |