Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000057279 | SCV000577340 | pathogenic | not provided | 2017-04-04 | criteria provided, single submitter | clinical testing | The N456K pathogenic variant in the LMNA gene was first reported in an individual with proximal muscle weakness, contractures, elevated CK levels, and use of a wheelchair at age 13 (Bonne et al., 2000). Functional studies indicate N456K disrupts the interaction amongst LMNA proteins (Dittmer et al., 2014). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N456K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and different missense variants at the same position (N456H/D/I) have been previously reported in association with muscular dystrophy (Astejada et al., 2007; Quijano-Roy et al., 2008). Additionally, missense variants in nearby residues (R453W/P; L454P; R455P; D461Y) have been reported in the Human Gene Mutation Database in association with LMNA-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057279 | SCV000088392 | not provided | not provided | no assertion provided | not provided |