Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041350 | SCV000065043 | likely pathogenic | Primary dilated cardiomyopathy | 2012-03-15 | criteria provided, single submitter | clinical testing | The Thr150Pro variant (LMNA) has been previously reported in 2 individuals with Emery-Dreifuss muscular dystrophy who also had conduction system disease and was absent from 160 control chromosomes (Felice 2000, Schamer 2011). Our laboratory has identified this variant in 1 out over >500 Caucasian probands with cardiomy opathy. The variant was present in 4 affected family members, supporting a patho genic role. Consistent with a laminopathy, clinical features in this family incl ude DCM, muscle weakness and conduction system disease. Threonine (Thr) at posit ion conserved in mammals, frog, and fish (lower species not available), which su ggests that a change may not be tolerated. Computational tools (AlignGVGD and SI FT) also support a pathogenic role, though their accuracy is unknown. In summary , this variant is considered to be likely pathogenic. |
| Ambry Genetics | RCV001265661 | SCV001443828 | pathogenic | Inborn genetic diseases | 2015-02-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001852841 | SCV002210700 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-02-02 | 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: 16218190). 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. ClinVar contains an entry for this variant (Variation ID: 48067). This missense change has been observed in individual(s) with Emery-Dreifuss muscular dystrophy and dilated cardiomyopathy (PMID: 10908904, 20848652, 24503780, 27532257; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 150 of the LMNA protein (p.Thr150Pro). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057407 | SCV000088520 | not provided | not provided | no assertion provided | not provided |