Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Al Jalila Children’s Genomics Center, |
RCV001733771 | SCV001984674 | uncertain significance | not specified | 2020-03-25 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001861044 | SCV002246963 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-11-29 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Leu38 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 1301822). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 38 of the LMNA protein (p.Leu38Phe). 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. |
School of Medicine, |
RCV003136132 | SCV003804972 | uncertain significance | Congenital muscular dystrophy due to LMNA mutation | no assertion criteria provided | research |