Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000656930 | SCV000225714 | uncertain significance | not provided | 2014-11-22 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000656930 | SCV000236114 | uncertain significance | not provided | 2023-06-13 | criteria provided, single submitter | clinical testing | In-frame deletion of 1 amino acids in a non-repeat region; Has been identified in five affected homozygous siblings from two consanguineous Middle Eastern families (ClinVar SCV000272211.3; ClinVar), which includes two homozygous infant siblings diagnosed with severe DCM that were previously described in an abstract by Al-Hassnan et al. (2013).; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26582918, 27535533) |
Laboratory for Molecular Medicine, |
RCV000183645 | SCV000272211 | uncertain significance | not specified | 2015-06-12 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Glu528del variant has been identified in 2 consanguineous families of Middle Eastern anc estry as homozygous in 5 affected siblings (Conference abstract by Al-Hassnan 20 13, LMM unpublished data). This variant has also been identified as heterozygous in 14/65856 European chromosomes by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org). This variant is a deletion of 1 amino acid at posi tion 528 from a string of 4 glutamic acids. It is unclear if this deletion will impact the protein. In summary, while there is some suspicion for a pathogenic r ole, the clinical significance of the p.Glu528del variant is uncertain. |
Invitae | RCV000647277 | SCV000769066 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2024-01-27 | criteria provided, single submitter | clinical testing | This variant, c.1582_1584del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Glu528del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs770868024, gnomAD 0.03%). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 31568572; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1572_1574delAGA (p.E525del). ClinVar contains an entry for this variant (Variation ID: 194130). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769827 | SCV000901253 | uncertain significance | Cardiomyopathy | 2020-05-13 | criteria provided, single submitter | clinical testing | |
Klaassen Lab, |
RCV000853115 | SCV000995826 | uncertain significance | Primary dilated cardiomyopathy | 2019-07-03 | criteria provided, single submitter | research | |
Mayo Clinic Laboratories, |
RCV000656930 | SCV002542274 | uncertain significance | not provided | 2021-07-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002390422 | SCV002703855 | uncertain significance | Cardiovascular phenotype | 2022-11-22 | criteria provided, single submitter | clinical testing | The c.1582_1584delGAA variant (also known as p.E528del) is located in coding exon 11 of the NEXN gene. This variant results from an in-frame GAA deletion at nucleotide positions 1582 to 1584. This results in the in-frame deletion of a glutamic acid at codon 528. This variant was reportedly detected in the homozygous state in two siblings with severe, pediatric onset dilated cardiomyopathy (Bruyndonckx L et al. Am J Med Genet A. 2021 08;185(8):2464-2470). This variant, also referred to as p.E525del, was detected in a homozygous proband with DCM and in the heterozygous state in a proband with DCM and noncompaction cardiomyopathy who was also homozygous for a variant in the TNNI3 gene (Kühnisch J. Clin Genet. 2019 12;96(6):549-559). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV000647277 | SCV002785898 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2021-09-08 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003338444 | SCV004046933 | uncertain significance | Dilated cardiomyopathy 1CC | criteria provided, single submitter | clinical testing | The inframe deletion c.1582_1584del (p.Glu528del) has been observed in individual(s) with dilated cardiomyopathy (Kuhnisch J, et.al.,2019).This variant has been reported to the ClinVar database as Uncertain Significance. The p.Glu528del variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.01535% is reported in gnomAD. This p.Glu528del causes deletion of amino acid Glutamic Acid at position 528. For these reasons, this variant has been classified as Uncertain Significance . | |
Diagnostic Laboratory, |
RCV000656930 | SCV001742865 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000183645 | SCV001919886 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000656930 | SCV001955753 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000656930 | SCV001964474 | likely benign | not provided | no assertion criteria provided | clinical testing |