ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.4982A>G (p.Lys1661Arg)

gnomAD frequency: 0.00006  dbSNP: rs761759361
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000423841 SCV000536658 uncertain significance not provided 2023-01-31 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Located in exon 38, which is reported as being expressed in a brain-specific transcript (Otto et al, 1991; Cunha et al, 2008; Wu et al, 2015); In silico analysis supports that this missense variant does not alter protein structure/function
Illumina Laboratory Services, Illumina RCV001148272 SCV001309157 uncertain significance Cardiac arrhythmia, ankyrin-B-related 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001297694 SCV001486722 uncertain significance Long QT syndrome 2021-02-23 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with ANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 393274). This variant is present in population databases (rs761759361, ExAC 0.002%). This sequence change replaces lysine with arginine at codon 1661 of the ANK2 protein (p.Lys1661Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine.
Ambry Genetics RCV002348252 SCV002645624 uncertain significance Cardiovascular phenotype 2023-01-20 criteria provided, single submitter clinical testing The c.4982A>G (p.K1661R) alteration is located in exon 38 (coding exon 38) of the ANK2 gene. This alteration results from a A to G substitution at nucleotide position 4982, causing the lysine (K) at amino acid position 1661 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000423841 SCV003818589 uncertain significance not provided 2021-04-19 criteria provided, single submitter clinical testing

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