Total submissions: 2
| 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. |
| Molecular Genetics Laboratory, |
RCV001173629 | SCV001336731 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |