Submissions for variant NM_001148.6(ANK2):c.10820A>G (p.Asn3607Ser)

dbSNP: rs367788127

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000170706	SCV000223259	uncertain significance	not provided	2014-05-18	criteria provided, single submitter	clinical testing	p.Asn3607Ser (AAC>AGC): c.10820 A>G in exon 40 of the ANK2 gene (NM_001148.4). The N3607S variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. The N3607S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although, the N3607S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties; the N3607 residue is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no mutations in nearby residues have been reported in association with LQTS. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LQT panel(s).
Ambry Genetics	RCV002426807	SCV002728001	uncertain significance	Cardiovascular phenotype	2019-01-29	criteria provided, single submitter	clinical testing	The p.N3607S variant (also known as c.10820A>G), located in coding exon 40 of the ANK2 gene, results from an A to G substitution at nucleotide position 10820. The asparagine at codon 3607 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002517635	SCV003249396	uncertain significance	Long QT syndrome	2022-03-15	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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 190575). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3607 of the ANK2 protein (p.Asn3607Ser).