Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000282505 | SCV000447231 | 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. |
Center for Advanced Laboratory Medicine, |
RCV000852982 | SCV000995731 | likely benign | Ventricular tachycardia | 2019-05-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001372879 | SCV001569571 | uncertain significance | Long QT syndrome | 2020-09-11 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 347347). This variant is present in population databases (rs773893598, ExAC 0.002%). This sequence change replaces glutamic acid with valine at codon 3767 of the ANK2 protein (p.Glu3767Val). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and valine. |
Ambry Genetics | RCV003168526 | SCV003856583 | uncertain significance | Cardiovascular phenotype | 2023-02-16 | criteria provided, single submitter | clinical testing | The p.E3767V variant (also known as c.11300A>T), located in coding exon 42 of the ANK2 gene, results from an A to T substitution at nucleotide position 11300. The glutamic acid at codon 3767 is replaced by valine, an amino acid with dissimilar 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. |