Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000490224 | SCV000577601 | likely pathogenic | not provided | 2016-09-29 | criteria provided, single submitter | clinical testing | The Gln207Stop likely pathogenic variant in the LMNA gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. Additionally, the Gln207Stop variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Gln207Stop is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LMNA gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014).While the Gln207Stop variant has not been published, it is expected to be pathogenic, However, other genetic and environmental factors influence disease expression and severity, and some individuals with a likely pathogenic variant may never become symptomatic. |
| Invitae | RCV003743751 | SCV004435176 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-01-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln207*) in the LMNA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 426996). |