ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2087dup (p.Asp697fs) (rs794728469)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182065 SCV000234368 pathogenic not provided 2017-01-05 criteria provided, single submitter clinical testing The c.3107dupG pathogenic variant in the KCNH2 gene has been published in association with LQTS. Berthet et al. (1999) identified the c.3107dupG pathogenic variant in four individuals in one family with LQTS. Splawski et al. (2000) reported that the c.3107dupG pathogenic variant was not identified in at least 400 control chromosomes, indicating it is not a common benign polymorphism. The c.3107_3108insG pathogenic variant in KCNH2 causes a shift in reading frame starting at codon Aspartic Acid 1037, changing it to an Arginine, and creates a premature stop codon at position 82 of the new reading frame, denoted p.Asp1037ArgfsX82. This pathogenic variant is expected to result in an abnormal, truncated protein or an absence of protein from this allele due to mRNA decay.
Ambry Genetics RCV000618925 SCV000737908 pathogenic Cardiovascular phenotype 2017-02-06 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000809575 SCV000949730 pathogenic Long QT syndrome 2018-10-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the KCNH2 gene (p.Asp1037Argfs*82). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 123 amino acids of the KCNH2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in several individuals affected with long QT syndrome or referred for long QT syndrome testing (PMID: 10086971, 23098067, 10973849, 11222472). This variant is also known as 3108+1G, insG3107-3108, and 3108insG in the literature. ClinVar contains an entry for this variant (Variation ID: 200803). This variant disrupts the C-terminus of the KCNH2 protein. Other variant(s) that disrupt this region (p.Ser1057Glufs*62, p.E1119*) have been observed in affected individuals (PMID: 19841300, 27920829). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.