Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000550500 | SCV000642324 | uncertain significance | Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S | 2017-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glutamic acid at codon 609 of the IGHMBP2 protein (p.Ala609Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the compound heterozygous state with a pathogenic variant (p.R570*) in an individual affected with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) (PMID: 22157136). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to conclusively determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Inherited Neuropathy Consortium | RCV000789973 | SCV000929362 | uncertain significance | Autosomal dominant distal hereditary motor neuropathy | no assertion criteria provided | literature only |