Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000800232 | SCV000939932 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2018-09-25 | 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. Experimental studies have shown that this missense change exhibits subcellular localization and aggregation defects in vitro as well as abnormal nuclear morphology in patient fibroblasts (PMID: 26098624). This variant has been observed to be de novo in an individual affected with congenital muscular dystrophy (PMID: 26098624). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 48 of the LMNA protein (p.Arg48Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. |
Gene |
RCV003235401 | SCV003933242 | pathogenic | not provided | 2022-12-12 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect as this variant results in abnormal protein aggregation (Tan et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10939567, 26098624, 32571898, 34240052) |