Submissions for variant NM_172056.2(KCNH2):c.545C>G (p.Ser182Trp) (rs1057517742)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000473446	SCV000543452	uncertain significance	Long QT syndrome	2018-09-12	criteria provided, single submitter	clinical testing	This sequence change replaces serine with tryptophan at codon 182 of the KCNH2 protein (p.Ser182Trp). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tryptophan. While this variant is not present in population databases (ExAC no frequency), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a KCNH2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease,Stanford University	RCV000786145	SCV000924817	uncertain significance	not provided	2016-09-19	no assertion criteria provided	provider interpretation