Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705582 | SCV000834584 | uncertain significance | Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S | 2018-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 565 of the IGHMBP2 protein (p.Asp565Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs770111639, ExAC 0.005%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with distal hereditary motor neuropathy, type VI (PMID: 15108294). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has been reported in combination with another IGHMBP2 variant in an individual affected with distal hereditary motor neuropathy, type VI (PMID: 22157136, 14681881). Experimental studies have shown that this missense change results in abolished helicase activity of the encoded IGHMBP2 protein (PMID: 19158098, 22157136). 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. |
| Biochemistry Laboratory of CDMU, |
RCV000768429 | SCV000899184 | likely pathogenic | Charcot-Marie-Tooth disease, axonal, type 2S | no assertion criteria provided | case-control | ||
| Inherited Neuropathy Consortium | RCV000790283 | SCV000929687 | uncertain significance | Distal spinal muscular atrophy | no assertion criteria provided | literature only |