Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000171813 | SCV000050824 | benign | Periodic paralysis | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000005879 | SCV000223524 | benign | not provided | 2018-07-13 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: none, 11207363, 11874988, 24055113, 12414843, 14504341, 15037716, 20051516) |
Ambry Genetics | RCV000253742 | SCV000318064 | likely benign | Cardiovascular phenotype | 2018-05-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
Centre for Mendelian Genomics, |
RCV000415218 | SCV000492900 | uncertain significance | Syncope; Ventricular fibrillation | 2014-07-03 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000223897 | SCV000539422 | uncertain significance | not specified | 2016-03-29 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Several pubs, including possible segs and functional studies, but frequency is too high for disease and wrong phenotype. ExAC: 0.4% (289/66352) European chromosomes |
Ce |
RCV000005879 | SCV000574898 | benign | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | KCNE3: BS1, BS2 |
Invitae | RCV000538199 | SCV000648490 | benign | Brugada syndrome 6 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000538199 | SCV000743882 | likely benign | Brugada syndrome 6 | 2014-10-09 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000538199 | SCV000884045 | likely benign | Brugada syndrome 6 | 2023-10-03 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852657 | SCV000995363 | likely benign | Cardiomyopathy | 2019-01-10 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000988595 | SCV001138374 | benign | Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000538199 | SCV001367235 | uncertain significance | Brugada syndrome 6 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. |
Mayo Clinic Laboratories, |
RCV000005879 | SCV001714385 | uncertain significance | not provided | 2020-07-15 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000223897 | SCV004803732 | likely benign | not specified | 2024-01-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000005879 | SCV000026061 | uncertain significance | not provided | 2007-04-01 | no assertion criteria provided | literature only | |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000223897 | SCV000280114 | uncertain significance | not specified | 2012-12-11 | 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. KCNE3 p.Arg83His Based on the data reviewed below we consider it a variant of uncertain significance, probably benign. The variant has been reported in cases of periodic paralysis (Abbot et al 2001, Dias Da Silva et al 2002, Sterberg et al 2003). However, it was then later found in controls, suggesting it is likely benign and was identified in these cases because it is present in 0.1-1% of all individuals (reviewed in more detail below). Hedley et al (2011) investigated the KCNE genes as putative HCM genes. In their cohort of 93 unrelated HCM patients two individuals had p.Arg83His in KCNE3. However, the authors concluded it was not causative since one of the patients also had a presumed pathogenic TNNT2 variant (specific variant not cited) and because of the prevalence in the general population. In silico analysis with PolyPhen-2 predicts the variant to be benign. The arginine at codon 83 is not conserved across species and in the marmoset is in fact a histidine. The KCNE3 gene has been associated with Brugada syndrome type 6 (Deplon et al 2008) and periodic paralysis (Abbott et al 2001). In total the variant has not been seen with allele frequencies of 0.1-1.1% in individuals in general population samples (rs17215437). Another variant, c.248G>T has been seen with allele frequencies of 0.14-1.52% in 1000 genomes. The variant was recently reported online in 50 of 5379 individuals in the NHLBI Exome Sequencing Project dataset (as of December 11th, 2012). The phenotype of those individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. |
Clinical Genetics, |
RCV000223897 | SCV001918148 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000005879 | SCV001956677 | likely benign | not provided | no assertion criteria provided | clinical testing |