Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000594075 | SCV000701771 | uncertain significance | not provided | 2016-09-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001867919 | SCV002184933 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-11-29 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of autosomal dominant LMNA-related muscular dystrophy (PMID: 29893365, 32571898; Invitae). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. 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: 497324). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 493 of the LMNA protein (p.Gln493Pro). |