Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000057216 | SCV000234692 | uncertain significance | not provided | 2020-02-21 | criteria provided, single submitter | clinical testing | Reported in one individual with cardiac conduction defects (CCD) as well as in several other similarly affected family members (Vytopil et a;., 2003) and in one individual with DCM and arrhythmia who also harbored the R331Q variant in LMNA (Benedetti et al., 2007); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Crystalization studies predict this variant impacts protein stability and may result in incorrect assembly of intermediate filaments (Bollati et al., 2012; Gangemi et al., 2013); This variant is associated with the following publications: (PMID: 31383942, 14684700, 17377071, 22326558, 23142632, 22266370, 25656816) |
| Invitae | RCV001049424 | SCV001213473 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-10-13 | 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. 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: 66760). This missense change has been observed in individuals with arrhythmogenic right ventricular dysplasia and dilated cardiomyopathy and/or conduction defects (PMID: 14684700, 17377071, 22326558, 25656816, 31383942). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 347 of the LMNA protein (p.Glu347Lys). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057216 | SCV000088329 | not provided | not provided | no assertion provided | not provided |