Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001038356 | SCV001201822 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2019-12-26 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.Gly232 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29893365, 10939567, 25982065, 23077635, 16772334, 29676528, 29753763). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in an individual affected with Emery-Dreifuss muscular dystrophy (PMID: 18564364, Invitae). ClinVar contains an entry for this variant (Variation ID: 66924). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 232 of the LMNA protein (p.Gly232Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |
Epithelial Biology; Institute of Medical Biology, |
RCV000057444 | SCV000088558 | not provided | not provided | no assertion provided | not provided | ||
Genome |
RCV001535783 | SCV001749941 | not provided | Primary dilated cardiomyopathy; Charcot-Marie-Tooth disease type 2B1; Benign scapuloperoneal muscular dystrophy with cardiomyopathy; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive | no assertion provided | phenotyping only | Variant interpreted as Likely pathogenic and reported on 12-27-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |