Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000227837 | SCV000291547 | likely benign | Charcot-Marie-Tooth disease type 2 | 2024-01-14 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000597022 | SCV000704294 | uncertain significance | not provided | 2016-12-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001184022 | SCV001349893 | uncertain significance | Cardiomyopathy | 2022-12-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 419 of the lamin A/C proteins. Computational prediction 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). Functional studies have shown that this variant may affect localization and binding affinity of the lamin A/C protein (PMID: 23977161, 24943589). This variant has been reported in three individuals from a single family affected with partial lipodystrophy and diabetes (PMID: 12716787). It has also been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 30847666). This variant has been identified in 6/282010 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, |
RCV002479935 | SCV002776935 | 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 | 2022-02-16 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003998891 | SCV004821879 | uncertain significance | Primary dilated cardiomyopathy | 2023-06-27 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 419 of the lamin A/C proteins. Computational prediction 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). Functional studies have shown that this variant may affect localization and binding affinity of the lamin A/C protein (PMID: 23977161, 24943589). This variant has been reported in three individuals from a single family affected with partial lipodystrophy and diabetes (PMID: 12716787). It has also been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 30847666). This variant has been identified in 6/282010 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 | RCV004020899 | SCV005030832 | uncertain significance | Cardiovascular phenotype | 2023-09-18 | criteria provided, single submitter | clinical testing | The p.R419C variant (also known as c.1255C>T), located in coding exon 7 of the LMNA gene, results from a C to T substitution at nucleotide position 1255. The arginine at codon 419 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in a family with familial partial lipodystrophy, and has been detected in an individual reported to have limb girdle muscular dystrophy (Haque WA et al. Diabetes Care, 2003 May;26:1350-5; Nishikawa A et al. J Med Genet, 2017 Feb;54:104-110). Functional studies indicate this variant may impact protein function (Kiel T et al. Int J Biochem Cell Biol, 2014 Aug;53:271-80). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |