Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001187072 | SCV001353731 | uncertain significance | Cardiomyopathy | 2023-07-24 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 98 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 not been reported in individuals affected with LMNA-related disorders in the literature. This variant has been identified in 1/31392 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. |
| Invitae | RCV001862947 | SCV002250596 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 98 of the LMNA protein (p.Glu98Gly). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 925242). 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 with a positive predictive value of 95%. 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. |
| Fulgent Genetics, |
RCV002484024 | SCV002786229 | 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 | 2021-10-02 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004008663 | SCV004844010 | uncertain significance | Primary dilated cardiomyopathy | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 98 of the lamin A/C proteins. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/31392 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. |