Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000506106 | SCV000604222 | pathogenic | not specified | 2017-01-26 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000802072 | SCV000941885 | pathogenic | Charcot-Marie-Tooth disease, type 2 | 2018-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 165 of the MFN2 protein (p.His165Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with dominant Charcot-Marie-Tooth disease in several families (PMID: 16714318, 24126688) and has also been observed in an individual affected with peripheral neuropathy (PMID:27549087). ClinVar contains an entry for this variant (Variation ID: 439897). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.His165 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 16835246, 16714318, 24819634, 17309650), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789411 | SCV000928766 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |