Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000535929 | SCV000642320 | likely pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S | 2017-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 580 of the IGHMBP2 protein (p.Val580Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs137852667, ExAC 0.03%). This variant has been reported in the compound heterozygous or homozygous state in families and individuals affected with spinal muscular atrophy with respiratory distress type 1 (PMID: 11528396, 16765827) and Charcot-Marie-Tooth disease type 2 (PMID: 25439726, 26392352). ClinVar contains an entry for this variant (Variation ID: 9114). Experimental studies have shown that this missense change impairs enzymatic activity in vitro (PMID: 22157136). In summary, this variant is a rare missense change that has been reported in affected individuals and shown to affect protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000664209 | SCV000029902 | pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 1 | 2001-09-01 | no assertion criteria provided | literature only | |
Gene |
RCV000192262 | SCV000239910 | pathogenic | Charcot-Marie-Tooth disease | 2015-04-30 | no assertion criteria provided | literature only | |
Institute of Human Genetics, |
RCV000664209 | SCV000787768 | pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 1 | 2018-04-25 | no assertion criteria provided | clinical testing |