Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Personalized Diabetes Medicine Program, |
RCV001174409 | SCV001337547 | uncertain significance | Monogenic diabetes | 2018-08-12 | criteria provided, single submitter | research | ACMG criteria: PP3 (REVEL 0.818 +10 predictors), PM2 (1 in gnomAD), BP5 (alternate cause)=VUS |
Invitae | RCV002558773 | SCV002957845 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-10-30 | criteria provided, single submitter | clinical testing | 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. 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: 917431). This missense change has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 31383942). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 502 of the LMNA protein (p.Ala502Thr). |