Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236185 | SCV000292586 | pathogenic | not provided | 2021-06-09 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with severe loss of enzymatic activity compared to wild type (Eckart et al., 2012); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22157136, 18802676, 26922252, 14681881, 21353777, 17431882, 14506069, 16964485, 23566544, 33210134, 25439726, 22965130, 24388491, 27535533) |
| Athena Diagnostics Inc | RCV000236185 | SCV000613764 | pathogenic | not provided | 2016-11-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000544728 | SCV000642295 | pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S | 2020-08-06 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 361 of the IGHMBP2 protein (p.Leu361Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs201060167, ExAC 0.01%). This variant has been reported in multiple individual with spinal muscular atrophy with respiratory distress type 1 as compound heterozygous with other loss-of-function or missense variants in IGHMBP2 gene (PMID: 14506069, 14681881) and in an individual with distal spinal muscular atrophy type 1 segregating with disease (PMID: 18802676). ClinVar contains an entry for this variant (Variation ID: 245627). Experimental evidence suggests that this variant results in a IGHMBP2 protein with loss of enzyme activity (PMID: 22157136). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000544728 | SCV000893230 | pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000790269 | SCV000929672 | uncertain significance | Distal spinal muscular atrophy | no assertion criteria provided | literature only | ||
| Inherited Neuropathy Consortium | RCV001027460 | SCV001190028 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | provider interpretation |