Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000686691 | SCV000814219 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2020-03-26 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Arg133 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12629077, 12927431, 14615128, 16174718). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LMNA protein function. This variant has been observed in individual(s) with Emery-Dreifuss muscular dystrophy (PMID: 11503164). ClinVar contains an entry for this variant (Variation ID: 14508). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 133 of the LMNA protein (p.Arg133Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. |
| OMIM | RCV000015602 | SCV000035867 | pathogenic | Emery-Dreifuss muscular dystrophy 2, autosomal dominant | 2003-08-09 | no assertion criteria provided | literature only | |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057398 | SCV000088511 | not provided | not provided | no assertion provided | not provided |