ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.827G>A (p.Arg276Lys)

gnomAD frequency: 0.00001  dbSNP: rs786205719
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170668 SCV000223221 uncertain significance not provided 2013-08-15 criteria provided, single submitter clinical testing .p.Arg276Lys (AGA>AAA): c.827 G>A in exon 9 of the ANK2 gene (NM_001148.4). The Arg276Lys variant in the ANK2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg276Lys results in a conservative amino acid substitution of one positively charged amino acid with another, at a position that is conserved across species. The Arg276Lys variant was not observed 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. However, no mutations in nearby residues have been reported in association with LQTS. With the clinical and molecular information available at this time, we cannot definitively determine if Arg276Lys is a disease-causing mutation or a rare benign variant. The variant is found in LQT panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001850431 SCV002182692 uncertain significance Long QT syndrome 2022-08-16 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"). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 276 of the ANK2 protein (p.Arg276Lys). This variant is present in population databases (rs786205719, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 190538).
Fulgent Genetics, Fulgent Genetics RCV002485056 SCV002794303 uncertain significance Cardiac arrhythmia, ankyrin-B-related 2021-08-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV004020024 SCV003896722 uncertain significance Cardiovascular phenotype 2023-07-10 criteria provided, single submitter clinical testing The p.R276K variant (also known as c.827G>A), located in coding exon 9 of the ANK2 gene, results from a G to A substitution at nucleotide position 827. The arginine at codon 276 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000170668 SCV004227018 uncertain significance not provided 2022-08-30 criteria provided, single submitter clinical testing

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