ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.7142C>A (p.Ala2381Asp)

gnomAD frequency: 0.00002  dbSNP: rs764841248
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000459302 SCV000545142 uncertain significance Long QT syndrome 2024-02-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2381 of the ANK2 protein (p.Ala2381Asp). This variant is present in population databases (rs764841248, gnomAD 0.004%). This missense change has been observed in individual(s) with Long QT Syndrome (PMID: 31737537). ClinVar contains an entry for this variant (Variation ID: 406472). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GeneDx RCV000521579 SCV000621682 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ANK2 gene. The A2381D variant has not been published as pathogenic or been reported as benign to our knowledge. The A2381D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The A2381D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species. Finally, in silico analysis predicts this variant likely does not alter the protein structure/function.
Ambry Genetics RCV000621967 SCV000737715 likely benign Cardiovascular phenotype 2024-04-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002481403 SCV002784605 uncertain significance Cardiac arrhythmia, ankyrin-B-related 2021-09-29 criteria provided, single submitter clinical testing

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