Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002390204 | SCV002699672 | likely pathogenic | Cardiovascular phenotype | 2022-05-13 | criteria provided, single submitter | clinical testing | The p.R471G variant (also known as c.1411C>G), located in coding exon 8 of the LMNA gene, results from a C to G substitution at nucleotide position 1411. The arginine at codon 471 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been reported in an individual with dilated cardiomyopathy (DCM) and cardiac conduction disease, as well as in two siblings with familial partial lipodystrophy (Muschke P et al. Am. J. Med. Genet. A, 2007 Dec;143A:2810-4; Ambry internal data). Another alteration at the same codon, p.R471H (c.1412G>A), has been reported in association with laminopathy and DCM (Astejada MN et al. Acta Myol. 2007; 26(3):159-64). This amino acid position is highly 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. |
| Invitae | RCV002514282 | SCV003523251 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-07-08 | criteria provided, single submitter | clinical testing | 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 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. This variant disrupts the p.Arg471 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18646565, 23582089, 27532257, 29943882). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 66824). This missense change has been observed in individual(s) with clinical features of autosomal dominant lipodystrophy (PMID: 18041775). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 471 of the LMNA protein (p.Arg471Gly). |
| Mayo Clinic Laboratories, |
RCV000057292 | SCV004224660 | uncertain significance | not provided | 2022-10-18 | criteria provided, single submitter | clinical testing | PP3, PM2_supporting |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057292 | SCV000088405 | not provided | not provided | no assertion provided | not provided |