Submissions for variant NM_001148.6(ANK2):c.10900G>A (p.Val3634Ile)

gnomAD frequency: 0.00002  dbSNP: rs143228029

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000467680	SCV000545146	uncertain significance	Long QT syndrome	2023-08-11	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ANK2 protein function. ClinVar contains an entry for this variant (Variation ID: 67598). This variant is also known as p.Val1516Ile. This missense change has been observed in individual(s) with long QT syndrome (PMID: 16253912). This variant is present in population databases (rs143228029, gnomAD 0.005%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 3634 of the ANK2 protein (p.Val3634Ile).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058343	SCV000089863	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:16253912). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.