Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000691928 | SCV000819727 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 343 of the LMNA protein (p.Arg343Gln). This variant is present in population databases (rs61177390, gnomAD 0.006%). 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: 66759). 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%. Experimental studies have shown that this missense change does not substantially affect LMNA function (PMID: 34862408). 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. |
| Color Diagnostics, |
RCV001180075 | SCV001344929 | uncertain significance | Cardiomyopathy | 2023-04-20 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 343 of the LMNA protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 28254189), as well as in four related individuals unaffected with LMNA-related conditions (PMID: 12467752). This variant has been identified in 10/282510 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, |
RCV002483087 | SCV002791701 | 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 | 2022-04-14 | criteria provided, single submitter | clinical testing | |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057215 | SCV000088328 | not provided | not provided | no assertion provided | not provided |