Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001066402 | SCV001231409 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 91 of the LMNA protein (p.Thr91Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 860145). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV002469339 | SCV002765224 | uncertain significance | not provided | 2022-12-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 10939567) |
| Fulgent Genetics, |
RCV002480424 | SCV002783223 | uncertain significance | Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome; Dilated cardiomyopathy 1A; Charcot-Marie-Tooth disease type 2B1; Emery-Dreifuss muscular dystrophy 2, autosomal dominant; Heart-hand syndrome, Slovenian type; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Mandibuloacral dysplasia with type A lipodystrophy; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive; Restrictive dermopathy 2 | 2021-08-27 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004000159 | SCV004828463 | uncertain significance | Primary dilated cardiomyopathy | 2023-12-01 | criteria provided, single submitter | clinical testing |