Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000680011 | SCV000807449 | pathogenic | Autosomal recessive distal spinal muscular atrophy 1 | 2017-09-01 | criteria provided, single submitter | clinical testing | This mutation has been previously reported as disease-causing and was found once in our laboratory homozygous in a 1-year-old male with congenital senseory and motor neuropathy, chronic respiratory failure, thrombocytopenia |
| Labcorp Genetics |
RCV001218953 | SCV001390864 | pathogenic | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2024-05-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg570*) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 14681881, 25439726, 25568292). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with spinal muscular atrophy with respiratory distress (SMARD) (PMID: 17431882). ClinVar contains an entry for this variant (Variation ID: 561032). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV000680011 | SCV002073179 | pathogenic | Autosomal recessive distal spinal muscular atrophy 1 | criteria provided, single submitter | clinical testing | The stop gained p.R570* in IGHMBP2 (NM_002180.3) has been reported in combination with a second IGHMBP2 variant in an individual affected with spinal muscular atrophy with respiratory distress (SMARD) (Ulf-Peter Guenther et al, 2007). The observed variant has been reported to ClinVar as Pathogenic. The p.R570* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Pathogenic. | |
| Inherited Neuropathy Consortium | RCV000790274 | SCV000929677 | uncertain significance | Distal spinal muscular atrophy | no assertion criteria provided | literature only | ||
| Genesis Genome Database | RCV000856973 | SCV000999539 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |