Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236185 | SCV000292586 | pathogenic | not provided | 2018-03-14 | criteria provided, single submitter | clinical testing | The L361P pathogenic variant in the IGHMBP2 gene has been reported previously in association with SMARD1 in multiple individuals who harbor a second pathogenic variant on the opposite IGHMBP2 allele (Pitt et al., 2003, Guenther et al., 2007; Guenther et al., 2009). The L361P variant is observed in 7/66,618 (0.01%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species. |
| 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 | 2019-12-13 | 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 |