Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000057243 | SCV000705992 | pathogenic | not provided | 2017-01-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000057243 | SCV001804717 | pathogenic | not provided | 2019-01-08 | criteria provided, single submitter | clinical testing | Observed in one family with Emery-Dreifuss muscular dystrophy (Bonne et al., 2000); Published functional studies demonstrate a damaging effect as RT-PCR analysis shows the variant results in two transcripts, one of normal size coding for the R386K missense variant and a larger mRNA coding for a truncated protein as a result of abnormal splicing (Bonne et al., 2000); Published functional studies demonstrate increased fractions of soluble mutant lamin A protein associated with nuclear deformation compared to wild-type and immunofluorescence showed significant aberrant localization of mutant LMNA in transfected cells (Zwerger et al., 2013; Ostlund et al., 2001); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 12783988, 12649505, 27884249, 23029315, 11792809, 23427149, 20848652, 10939567) |
| Invitae | RCV003581572 | SCV004292920 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-02-02 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg386 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23427149; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 66782). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 386 of the LMNA protein (p.Arg386Lys). This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant muscular dystrophy (PMID: 10939567, 27884249, 31069529). It has also been observed to segregate with disease in related individuals. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change is associated with altered splicing resulting in unknown protein product impact (PMID: 10939567). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057243 | SCV000088356 | not provided | not provided | no assertion provided | not provided |