ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.2005G>T (p.Glu669Ter) (rs1588143112)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001205278 SCV001376523 likely pathogenic Charcot-Marie-Tooth disease type 2P 2019-09-23 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the LRSAM1 gene (p.Glu669*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acids of the LRSAM1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Charcot-Marie-Tooth disease (Invitae). This variant disrupts the RING of the LRSAM1 protein, which mediates ubiquitylation (PMID: 24894446, 28335037). While functional studies have not been performed to directly test the effect of this variant on LRSAM1 protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genesis Genome Database RCV000857216 SCV000999800 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.