Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000462640 | SCV000548858 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-03-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects LMNA function (PMID: 20160190, 24623722). 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: 66884). This missense change has been observed in individuals with Emery–Dreifuss muscular dystrophy and dilated cardiomyopathy (PMID: 12628721, 20160190, 21922471, 23582089, 23702046, 26567375). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 89 of the LMNA protein (p.Arg89Leu). |
Epithelial Biology; Institute of Medical Biology, |
RCV000057383 | SCV000088496 | not provided | not provided | no assertion provided | not provided |