Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000057431 | SCV000234676 | likely pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | Reported in one individual diagnosed with generalized skeletal muscle involvement and cardiac conduction disease at the age of 57 (Scharner et al., 2011); Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 10939567, 26659599, 20848652, 35242549, 34862408) |
| Eurofins Ntd Llc |
RCV000057431 | SCV000703083 | uncertain significance | not provided | 2016-12-22 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000694277 | SCV000822713 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 206 of the LMNA protein (p.Phe206Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant LMNA-related conditions (PMID: 20848652; Invitae). ClinVar contains an entry for this variant (Variation ID: 66916). 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. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002354249 | SCV002657350 | pathogenic | Cardiovascular phenotype | 2021-12-02 | criteria provided, single submitter | clinical testing | The p.F206L pathogenic mutation (also known as c.618C>G), located in coding exon 3 of the LMNA gene, results from a C to G substitution at nucleotide position 618. The phenylalanine at codon 206 is replaced by leucine, an amino acid with highly similar properties. This variant has been detected in multiple individuals affected with laminopathy phenotypes, including limb-girdle muscular dystrophy (LGMD), dilated cardiomyopathy (DCM), and/or arrhythmias, and co-segregation has been reported in at least three families (Scharner J et al. Hum. Mutat., 2011 Feb;32:152-67; GeneDx pers comm; Invitae pers. comm.). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Revvity Omics, |
RCV000057431 | SCV003816982 | likely pathogenic | not provided | 2023-09-07 | criteria provided, single submitter | clinical testing | |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057431 | SCV000088545 | not provided | not provided | no assertion provided | not provided |