Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, |
RCV001095539 | SCV001251041 | likely pathogenic | Autosomal recessive distal spinal muscular atrophy 1 | 2020-03-31 | criteria provided, single submitter | research | |
| 3billion | RCV000664227 | SCV002059002 | pathogenic | Charcot-Marie-Tooth disease axonal type 2S | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000009113, PMID:11528396, PS1_S). The variant has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 11528396,PM3_P). It was co-segregated with Charcot-Marie-Tooth disease, axonal, type 2S in multiple affected family members with additional meioses meeting moderate evidence levels (PMID: 11528396, PP1_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.931, 3CNET: 0.887, PP3_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Revvity Omics, |
RCV003488333 | SCV004238246 | likely pathogenic | not provided | 2023-03-15 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003764541 | SCV004570795 | pathogenic | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2023-05-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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: 9113). This missense change has been observed in individual(s) with spinal muscular atrophy with respiratory distress (PMID: 11528396). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 213 of the IGHMBP2 protein (p.His213Arg). |
| OMIM | RCV001095539 | SCV000029901 | pathogenic | Autosomal recessive distal spinal muscular atrophy 1 | 2023-10-17 | no assertion criteria provided | literature only | |
| Institute of Human Genetics, |
RCV000664227 | SCV000787792 | pathogenic | Charcot-Marie-Tooth disease axonal type 2S | 2018-04-25 | no assertion criteria provided | clinical testing |