Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001704886 | SCV000236148 | uncertain significance | not provided | 2023-04-03 | criteria provided, single submitter | clinical testing | Reported in an individual with DCM (Gigli et al., 2019); described as c.1416_1418delAAG (p.Arg475del); In-frame deletion of one amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 31514951) |
Ambry Genetics | RCV000249380 | SCV000318850 | likely benign | Cardiovascular phenotype | 2020-09-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV000458753 | SCV000549235 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2023-12-11 | criteria provided, single submitter | clinical testing | This variant, c.1419_1421del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Arg475del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs766608869, gnomAD 0.02%). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 31514951). ClinVar contains an entry for this variant (Variation ID: 201940). 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. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000845464 | SCV000987555 | uncertain significance | Primary familial dilated cardiomyopathy | criteria provided, single submitter | clinical testing | ||
CHEO Genetics Diagnostic Laboratory, |
RCV001170730 | SCV001333333 | uncertain significance | Cardiomyopathy | 2019-03-01 | criteria provided, single submitter | clinical testing | |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000183679 | SCV000280399 | uncertain significance | not specified | 2013-05-22 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p. Arg474del (c.1419_1421delAAG) This variant is novel. This variant is located in exon 11 (coding exon 10) of the NEXN gene. The variant results from an in-frame AAG deletion between nucleotide position 1419 and 1421. This results in the deletion of an arginine residue at codon 474. The arginine at codon 474 is conserved across species, as are neighboring amino acids. In total the variant has not been seen in ~6,500 published controls and individuals from publicly available population datasets. There is no variation at codon 474 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 8/1/13). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 8/1/13). Ambry genetics did not include internal control data. |