Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000593400 | SCV000706446 | uncertain significance | not provided | 2017-02-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000693354 | SCV000821220 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-08-31 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 500476). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is present in population databases (rs746056534, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 285 of the LMNA protein (p.Val285Leu). |
| Color Diagnostics, |
RCV001189490 | SCV001356797 | uncertain significance | Cardiomyopathy | 2019-09-18 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with leucine at codon 285 of the LMNA protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). 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 1/251086 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, |
RCV002483624 | SCV002775401 | 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 | 2021-08-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004024792 | SCV005030841 | uncertain significance | Cardiovascular phenotype | 2024-03-12 | criteria provided, single submitter | clinical testing | The p.V285L variant (also known as c.853G>T), located in coding exon 5 of the LMNA gene, results from a G to T substitution at nucleotide position 853. The valine at codon 285 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |