Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156465 | SCV000206184 | uncertain significance | not specified | 2014-04-04 | criteria provided, single submitter | clinical testing | The p.Lys78Asn variant in LMNA has been identified in 1 individual with DCM and atrial fibrillation (LMM data) and was absent from large population studies. Com putational prediction tools and conservation analysis suggest that the variant m ay impact the protein, though this information is not predictive enough to deter mine pathogenicity. In summary, the clinical significance of this variant is unc ertain. ACMG/AMP Criteria applied: PM2, PP3, PP4. |
| Invitae | RCV003581579 | SCV004292901 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 78 of the LMNA protein (p.Lys78Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 27884249, 36548481). ClinVar contains an entry for this variant (Variation ID: 179669). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |