Submissions for variant NM_000238.4(KCNH2):c.2246G>T (p.Gly749Val)

dbSNP: rs199472989

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181844	SCV000234147	pathogenic	not provided	2014-02-25	criteria provided, single submitter	clinical testing	p.Gly749Val (GGC>GTC): c.2246 G>T in exon 9 of the KCNH2 gene (NM_000238.2)The G749V mutation in the KCNH2 gene has been reported previously in association with LQTS. The G749V mutation was reported in one patient with LQTS, and was not detected in >2,600 reference alleles (Kapplinger et al., 2009). Other missense mutations affecting nearby residues (R744P, R752Q) have been reported in association with LQTS, supporting the functional importance of this region of the protein. Furthermore, the G749V mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, G749V in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000454509	SCV000539432	uncertain significance	not specified	2016-03-31	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: Reported in 1 proband; Absent from ExAC with good coverage; ClinVar: 1 pathogenic
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058098	SCV000089618	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:19716085;PMID:19841300). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.