Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000621498 | SCV000737998 | uncertain significance | Cardiovascular phenotype | 2022-03-14 | criteria provided, single submitter | clinical testing | The p.N283S variant (also known as c.848A>G), located in coding exon 5 of the LMNA gene, results from an A to G substitution at nucleotide position 848. The asparagine at codon 283 is replaced by serine, an amino acid with highly similar properties. This variant was detected in a cohort of patients with with sporadic inclusion body myositis, and was possibly associated with Emery-Dreifuss muscular dystrophy; however, clinical details were not provided (Weihl CC et al. Neuromuscul Disord. 2015;25:289-96). This amino acid position is not well conserved in available vertebrate species, and serine 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. |
Invitae | RCV000701219 | SCV000830010 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 283 of the LMNA protein (p.Asn283Ser). This variant is present in population databases (rs765241364, gnomAD 0.006%). This missense change has been observed in individual(s) with inclusion body myositis (PMID: 25617006). This variant is also known as N171S. ClinVar contains an entry for this variant (Variation ID: 519439). 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. 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. |
Eurofins Ntd Llc |
RCV000733487 | SCV000861563 | uncertain significance | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV001172626 | SCV001335689 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Color Diagnostics, |
RCV001187553 | SCV001354373 | uncertain significance | Cardiomyopathy | 2023-01-03 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 283 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 inclusion body myositis (PMID: 25617006) and in an individual affected with familial partial lipodystrophy type 2 (doi:10.1210/jendso/bvab048.069). This variant has been identified in 8/282512 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. |
Gene |
RCV000733487 | SCV001769716 | uncertain significance | not provided | 2023-10-06 | criteria provided, single submitter | clinical testing | Reported, using alternative nomenclature (N171S), in a patient with inclusion body myositis; however, this individual also harbored a variant in the EMD gene (Weihl et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25617006, 10939567) |
Fulgent Genetics, |
RCV002506508 | SCV002812202 | 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 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000733487 | SCV003814736 | uncertain significance | not provided | 2022-08-04 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004002692 | SCV004846228 | uncertain significance | Primary dilated cardiomyopathy | 2023-12-18 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 283 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 inclusion body myositis (PMID: 25617006) and in an individual affected with familial partial lipodystrophy type 2 (doi:10.1210/jendso/bvab048.069). This variant has been identified in 8/282512 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. |