Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000808152 | SCV000948246 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-09-23 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 296 of the LMNA protein (p.Arg296Cys). This variant is present in population databases (rs375987939, gnomAD 0.006%). This missense change has been observed in individual(s) with myofibrillar myopathy (PMID: 27633507). ClinVar contains an entry for this variant (Variation ID: 652575). 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. |
| Color Diagnostics, |
RCV001188707 | SCV001355840 | uncertain significance | Cardiomyopathy | 2023-01-26 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 296 of the LMNA protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a family affected with myofibrillar myopathy and cardiac arrhythmia (Avila-Smirnow et al. P2.18 poster, 2018). It has also been reported in individuals affected with chronic kidney disease (PMID: 31383942). This variant has been identified in 3/250462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002487736 | SCV002789679 | 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 | 2022-04-22 | criteria provided, single submitter | clinical testing |