Submissions for variant NM_172056.2(KCNH2):c.298C>G (p.Arg100Gly) (rs121912515)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181948	SCV000234251	pathogenic	not provided	2012-04-25	criteria provided, single submitter	clinical testing	p.Arg100Gly (CGG>GGG): c.298 C>G in exon 2 of the KCNH2 gene (NM_000238.2). The Arg100Gly mutation in the KCNH2 gene has been reported in association with LQTS. Millat G et al. described a 41 year-old patient with a prolonged QT interval and history of torsade de pointes leading to ventricular fibrillation during exercise who harbored the Arg100Gly mutation in the KCNH2 gene as well as the Asp1819Asn mutation in the SCN5A gene. The authors reported both mutations were absent from 200 control chromosomes. Additionally, other mutations at the same codon (Arg100Gln, Arg100Trp) and nearby codons (Tyr99Ser, Lys101Glu, Asp102Ala, Asp102Val) have been reported in association with LQTS, supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Arg100Gly was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating is not a common variant in these populations.Therefore, Arg100Gly in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Ambry Genetics	RCV000617723	SCV000738245	uncertain significance	Cardiovascular phenotype	2017-11-28	criteria provided, single submitter	clinical testing	Insufficient evidence
OMIM	RCV000015525	SCV000035790	pathogenic	Long QT syndrome 2/3, digenic	2006-09-01	no assertion criteria provided	literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust	RCV000058186	SCV000089706	not provided	Congenital long QT syndrome		no assertion provided	literature only	This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16922724). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.