Submissions for variant NM_001148.6(ANK2):c.11516G>C (p.Ser3839Thr)

gnomAD frequency: 0.00004  dbSNP: rs148654834

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001572006	SCV001796577	uncertain significance	not provided	2019-05-24	criteria provided, single submitter	clinical testing	Reported in one Caucasian female from a cohort of individuals referred for LQTS genetic testing (described as S1721T due to the use of alternate nomenclature); however, this individual also harbored a pathogenic variant in the KCNJ2 gene and no additional clinical details or segregation studies were reported (Sherman et al., 2005); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16253912, 22581653)
Invitae	RCV001854214	SCV002193174	uncertain significance	Long QT syndrome	2023-04-05	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 67601). This variant is also known as S1721T. This missense change has been observed in individual(s) with long QT syndrome (PMID: 16253912). This variant is present in population databases (rs148654834, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 3839 of the ANK2 protein (p.Ser3839Thr). 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.
Fulgent Genetics, Fulgent Genetics	RCV002504967	SCV002815608	uncertain significance	Cardiac arrhythmia, ankyrin-B-related	2022-01-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003343628	SCV004061335	uncertain significance	Inborn genetic diseases	2023-08-04	criteria provided, single submitter	clinical testing	The c.11516G>C (p.S3839T) alteration is located in exon 43 (coding exon 43) of the ANK2 gene. This alteration results from a G to C substitution at nucleotide position 11516, causing the serine (S) at amino acid position 3839 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058348	SCV000089868	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.