Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156173 | SCV000205889 | likely pathogenic | Primary dilated cardiomyopathy | 2013-11-08 | criteria provided, single submitter | clinical testing | The Ala434X variant in LMNA has not been reported in individuals with cardiomyop athy and data from large population studies are insufficient to assess the frequ ency of this variant in the general population. This variant introduces a deleti on of 8 bases and creates a premature termination codon at amino acid 434. This alteration is predicted to lead to a truncated or absent protein. Heterozygous l oss of function of the LMNA gene is an established disease mechanism for DCM. In summary, this variant is likely to be pathogenic, but additional studies are ne eded to fully establish its clinical significance. |
| Invitae | RCV001850150 | SCV002214410 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2020-11-03 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with LMNA-related conditions (PMID: 27884249). ClinVar contains an entry for this variant (Variation ID: 179384). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala434*) 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). For these reasons, this variant has been classified as Pathogenic. |