Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Diagnostics Lab, |
RCV000498809 | SCV000590850 | uncertain significance | not specified | 2017-01-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001068853 | SCV001233986 | likely pathogenic | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2023-06-17 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IGHMBP2 protein function. ClinVar contains an entry for this variant (Variation ID: 433162). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 29858556, 32709422; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 508 of the IGHMBP2 protein (p.Ser508Leu). |
| Mendelics | RCV002248737 | SCV002516574 | pathogenic | Autosomal recessive distal spinal muscular atrophy 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000664228 | SCV000787793 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2S | 2018-04-25 | no assertion criteria provided | clinical testing | |
| Genesis Genome Database | RCV000856971 | SCV000999537 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |