Submissions for variant NM_000238.4(KCNH2):c.139G>T (p.Gly47Cys)

dbSNP: rs794728409

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181929	SCV000234232	pathogenic	not provided	2012-08-12	criteria provided, single submitter	clinical testing	p.Gly47Cys (GGC>TGC):c.139 G>T in exon 2 of the KCNH2 gene (NM_000238.2). The Gly47Cys mutation in the KCNH2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. However, a mutation affecting this same codon, (Gly47Val), has been reported in association with LQTS (Splawski I et al., 2000; Moss A et al., 2002). Mutations in nearby residues (Asn45Tyr, Cys49Tyr) have also been reported in association with LQTS, further supporting the functional importance of this codon and this region of the protein. Gly47Cys results in a non-conservative amino acid substitution of non-polar, small Glycine with a neutral, polar Cysteine at a position that is conserved across species. Furthermore, the NHLBI ESP Exome Variant Server reports Gly47Cys was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.In summary, Gly47Cys in the KCNH2 gene is interpreted as a likely disease-causing mutation. The variant is found in LQT panel(s).
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV001248792	SCV001422304	likely pathogenic	Long QT syndrome 2	2019-12-19	criteria provided, single submitter	clinical testing