Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000218886 | SCV000271922 | uncertain significance | not specified | 2015-06-24 | criteria provided, single submitter | clinical testing | The p.Thr436Ala variant in LMNA has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction to ols and conservation analysis do not provide strong support for or against an im pact to the protein. In summary, the clinical significance of the p.Thr436Ala va riant is uncertain. |
Invitae | RCV000824027 | SCV000964902 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 436 of the LMNA protein (p.Thr436Ala). This variant is present in population databases (no rsID available, 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: 228802). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 |
RCV001753644 | SCV001986744 | uncertain significance | not provided | 2023-04-13 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 10939567) |
Color Diagnostics, |
RCV001804951 | SCV002052085 | uncertain significance | Cardiomyopathy | 2021-12-20 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 436 of the lamin A/C proteins. 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/249682 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. |
Ambry Genetics | RCV002381743 | SCV002691344 | uncertain significance | Cardiovascular phenotype | 2021-02-23 | criteria provided, single submitter | clinical testing | The p.T436A variant (also known as c.1306A>G), located in coding exon 7 of the LMNA gene, results from an A to G substitution at nucleotide position 1306. The threonine at codon 436 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002503855 | SCV002815069 | 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 | 2022-04-27 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001753644 | SCV003814728 | uncertain significance | not provided | 2020-09-08 | criteria provided, single submitter | clinical testing |