Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001382394 | SCV001581146 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-06-22 | 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). 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: 65764). This missense change has been observed in individual(s) with conduction disease and/or dilated cardiomyopathy (PMID: 12486434). 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 leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 215 of the LMNA protein (p.Leu215Pro). |
| Ambry Genetics | RCV002362688 | SCV002659637 | likely pathogenic | Cardiovascular phenotype | 2021-05-11 | criteria provided, single submitter | clinical testing | The p.L215P variant (also known as c.644T>C), located in coding exon 4 of the LMNA gene, results from a T to C substitution at nucleotide position 644. The leucine at codon 215 is replaced by proline, an amino acid with similar properties. This alteration has been detected in a family with cardiac conduction defects and dilated cardiomyopathy (DCM), showing segregation within the family (Hershberger RE et al. Am Heart J, 2002 Dec;144:1081-6). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Bunick CG et al. J Invest Dermatol, 2017 01;137:142-150). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Gene |
RCV000056000 | SCV000087056 | not provided | Dilated cardiomyopathy 1A | no assertion provided | literature only | ||
| Epithelial Biology; Institute of Medical Biology, |
RCV000057438 | SCV000088552 | not provided | not provided | no assertion provided | not provided |