ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.6973G>C (p.Asp2325His)

gnomAD frequency: 0.00004  dbSNP: rs1298469624
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619857 SCV000735547 likely benign Cardiovascular phenotype 2020-10-06 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779698 SCV000916451 uncertain significance not specified 2018-06-11 criteria provided, single submitter clinical testing Variant summary: ANK2 c.6973G>C (p.Asp2325His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.2e-05 in 276420 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6973G>C in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000806581 SCV000946586 uncertain significance Long QT syndrome 2020-03-03 criteria provided, single submitter clinical testing 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ANK2-related disease. ClinVar contains an entry for this variant (Variation ID: 518570). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 2325 of the ANK2 protein (p.Asp2325His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. 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.

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