Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000465598 | SCV000548861 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2018-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 456 of the LMNA protein (p.Asn456Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in a population databases (rs267607599), however, there is no reported allele frequency. This variant has been reported in 2  individuals affected with early onset myopathy and Emery-Dreifuss muscular dystrophy (PMID: 18551513, 21520333). This variant has been shown to arise de novo in individuals affected with early onset myopathy (PMID: 18551513). ClinVar contains an entry for this variant (Variation ID: 66811). Different missense substitutions at this codon (p.Asn456His, p.Asn456Ile, p.Asn456Lys) are reported to be deleterious (PMID: 24623722, 10939567, 18646565, 11973618, 21632249, 20980393, 22186027, 25996830). This indicates that the asparagine residue is important for lamin A/C protein function. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000057277 | SCV001248557 | pathogenic | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000057277 | SCV002552745 | pathogenic | not provided | 2022-01-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 10939567, 27363342, 24375749, 24623722, 34240052, 32571898, 18551513) |
Epithelial Biology; Institute of Medical Biology, |
RCV000057277 | SCV000088390 | not provided | not provided | no assertion provided | not provided |