Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172002 | SCV000054719 | uncertain significance | Emery-Dreifuss muscular dystrophy | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000041313 | SCV000065005 | uncertain significance | not specified | 2017-05-23 | criteria provided, single submitter | clinical testing | The p.Arg401Cys variant in LMNA has been reported in 1 individual with Emery Dre ifuss muscular dystrophy who carried a second LMNA variant (p.Thr150fs), which w as also present in the father who suffered sudden cardiac death. The p.Arg401Cys variant was also identified in the reportedly unaffected mother and sister (Han isch 2002, Vytopil 2002, Muchir 2004, Emerson 2009). This variant was also ident ified in 2 individuals with DCM (one with neonatal onset), segregated with disea se in 1 affected relative (Chami 2014, LMM data) and has also been reported in C linVar (Variation ID 48035). It has been identified in 6/34400 of Latino chromos omes and 11/126264 of European chromosomes by the Genome Aggregation Consortium (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs61094188). Computational pred iction tools and conservation analysis do not provide strong support for or agai nst an impact to the protein. In summary, the clinical significance of the p.Arg 401Cys variant is uncertain. |
Gene |
RCV000057258 | SCV000234697 | uncertain significance | not provided | 2023-05-30 | criteria provided, single submitter | clinical testing | Observed in trans with another LMNA variant (c.447insC) in a different individual with EDMD and was found to be inherited from a parent without neuromuscular disease (Emerson, et al., 2009); Observed in two siblings with dilated cardiomyopathy who may or may not have had additional variants in other cardiomyopathy-related genes (Chami et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23977161, 12376891, 25210889, 15843404, 23861362, 16584978, 24503780, 24623722, 28531892, 27532257, 17107595, 15372542, 30420677, 31428229, 34426522, 19524666, 25448463, 32880476, 31383942, 32793522, 12467752, 34240052, 32041611, 32376792, 10939567, 30564623) |
Eurofins Ntd Llc |
RCV000057258 | SCV000337619 | uncertain significance | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000528639 | SCV000657795 | likely benign | Charcot-Marie-Tooth disease type 2 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000627127 | SCV000747935 | likely pathogenic | Primary familial dilated cardiomyopathy | 2020-07-10 | criteria provided, single submitter | clinical testing | PM2;PP1 (internal data); PP2;PP3;PS4_supp |
CHEO Genetics Diagnostic Laboratory, |
RCV000769728 | SCV000901149 | uncertain significance | Cardiomyopathy | 2015-09-30 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV001172616 | SCV001335679 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Color Diagnostics, |
RCV000769728 | SCV001355731 | uncertain significance | Cardiomyopathy | 2023-02-15 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 401 of the lamin A/C protein. 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). This variant is located in the C-terminal region of the protein that mediates interaction with many protein binding partners. Functional studies have shown that for the most part, this variant does not adversely affect protein interaction, although interaction with some binding partners may be affected (PMID: 23977161, 24623722, 32698523). This variant has been reported in an individual affected with Hauptmann-Thannhauser muscular dystrophy (PMID: 12376891), in a family and an unrelated individual affected with dilated cardiomyopathy (PMID: 25448463, 32880476), and in another individual affected with congenital heart defects (PMID: 32793522). This variant has also been identified in 22/280520 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. |
Mayo Clinic Laboratories, |
RCV000057258 | SCV001715573 | uncertain significance | not provided | 2023-06-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345327 | SCV002653838 | uncertain significance | Cardiovascular phenotype | 2021-11-18 | criteria provided, single submitter | clinical testing | The p.R401C variant (also known as c.1201C>T), located in coding exon 7 of the LMNA gene, results from a C to T substitution at nucleotide position 1201. The arginine at codon 401 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was originally reported in an individual with skeletal, muscular, and cardiac findings, as well as in his unaffected mother and sister (Hanisch F et al. Nervenarzt, 2002 Oct;73:1004-11; Vytopil M et al. Neuromuscul. Disord., 2002 Dec;12:958-63). This variant has also been detected in individuals with Emery-Dreifuss muscular dystrophy, including one case of a compound heterozygote who also had an LMNA truncating variant (Muchir A et al. Muscle Nerve, 2004 Oct;30:444-50; Emerson LJ et al. Biochim. Biophys. Acta, 2009 Aug;1792:810-21). In addition, this variant has been described in individuals and genetic testing cohorts with dilated cardiomyopathy, including two affected siblings, but clinical details were limited (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8; Chami N et al. Can J Cardiol, 2014 Dec;30:1655-61; Walsh R et al. Genet. Med., 2017 02;19:192-203; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 10;13:476-487). Finally, this variant was reported as maternally inherited in a left ventricular non-compaction (LVNC) case with a maternal family history of atrial fibrillation and sudden cardiac death, but whose carrier mother was apparently unaffected (Baban A et al. Front Pediatr, 2020 Jul;8:374). Functional studies have suggested this alteration may impact protein function; however, the clinical relevance of those results is unclear (Muchir A et al. Muscle Nerve, 2004 Oct;30:444-50; Capanni C et al. Exp. Cell Res., 2003 Nov;291:122-34; Yang L et al. PLoS ONE, 2013 Aug;8:e71850; Angori S et al. Cell. Physiol. Biochem., 2017 May;42:169-184). This amino acid position is well 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. |
Revvity Omics, |
RCV000057258 | SCV003814685 | uncertain significance | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000057258 | SCV004124989 | uncertain significance | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | LMNA: PS1, PM6:Supporting, PP4, PS3:Supporting, BS1 |
Epithelial Biology; Institute of Medical Biology, |
RCV000057258 | SCV000088371 | not provided | not provided | no assertion provided | not provided | ||
Blueprint Genetics | RCV000157295 | SCV000207027 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2014-08-19 | no assertion criteria provided | clinical testing | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000057258 | SCV001959775 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000057258 | SCV001966908 | uncertain significance | not provided | no assertion criteria provided | clinical testing |