Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000691173 | SCV000818919 | uncertain significance | Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S | 2018-02-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 595 of the IGHMBP2 protein (p.Arg595Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs143766075, ExAC 0.01%). This variant has not been reported in the literature in individuals with IGHMBP2-related disease. 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: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg595Trp) has been reported in combination with another IGHMBP2 variant in an individual affected with Charcot–Marie–Tooth disease, type 2S (PMID: 28202949). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |