Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Lupski Lab, |
RCV000235074 | SCV000292347 | likely pathogenic | Cowchock syndrome | 2015-08-18 | criteria provided, single submitter | research | Likely pathogenic based on conservation and prediction scores (Phylop, Polyphen, SIFT, MutationTaster) and consistent with neuropathy of patient. Patient also had Sotos syndrome with de novo frameshift insertion in NSD1 |
Invitae | RCV000538656 | SCV000658927 | uncertain significance | Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency | 2019-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with isoleucine at codon 463 of the AIFM1 protein (p.Arg463Ile). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and isoleucine. This variant is present in population databases (rs202219398, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Charcot-Marie-Tooth 2 disease (PMID: 26257172); however, a disease-causing variant in an unrelated gene was also identified in this individual. ClinVar contains an entry for this variant (Variation ID: 243069). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on AIFM1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV000837953 | SCV000979815 | likely benign | not provided | 2018-05-01 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |