Submissions for variant NM_000238.4(KCNH2):c.656A>T (p.Asp219Val)

gnomAD frequency: 0.00002  dbSNP: rs587777907

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001234187	SCV001406819	uncertain significance	Long QT syndrome	2022-03-13	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 219 of the KCNH2 protein (p.Asp219Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with long QT syndrome (PMID: 25914329). ClinVar contains an entry for this variant (Variation ID: 157662). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects KCNH2 function (PMID: 25914329). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Dept of Medical Biology, Uskudar University	RCV001234187	SCV004022001	uncertain significance	Long QT syndrome	2024-01-08	criteria provided, single submitter	research	Criteria: PM2, PP2
McDonald Lab; Albert Einstein College of Medicine	RCV000144957	SCV000191968	pathogenic	Long QT syndrome 2		no assertion criteria provided	research