ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.2019dup (p.Glu674fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806958 SCV000946982 pathogenic Charcot-Marie-Tooth disease type 2P 2018-11-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the LRSAM1 gene (p.Glu674Argfs*83). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acids of the LRSAM1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LRSAM1-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acids is currently unknown. A different frameshift variant in the last exon (p.Leu708Argfs*28) has been determined to be pathogenic (PMID: 22012984, 28335037) and another similar frameshift variant (p.Ile713Serfs*20) has been observed in individuals affected with Charcot-Marie-Tooth disease type 2 (PMID: 26752306). This suggests that disruption of this region is critical for LRSAM1 protein function and that other extensions in the last exon may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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.