Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000364664 | SCV000447161 | uncertain significance | Cardiac arrhythmia, ankyrin-B-related | 2018-01-12 | 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. |
| Gene |
RCV001753818 | SCV002005138 | uncertain significance | not provided | 2024-03-29 | criteria provided, single submitter | clinical testing | Reported in a 61 year old male with syncope, bradycardia, QT prolongation on epinephrine challenge, non-sustained ventricular tachycardia, and a family history of sudden death; however, this individual also harbored a variant in the KCNE1 gene (PMID: 27784853); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 27785597, 27784853) |
| Ambry Genetics | RCV004639224 | SCV005134142 | uncertain significance | Cardiovascular phenotype | 2024-06-04 | criteria provided, single submitter | clinical testing | The p.G761S variant (also known as c.2281G>A), located in coding exon 21 of the ANK2 gene, results from a G to A substitution at nucleotide position 2281. The glycine at codon 761 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. According to data from gnomAD, the frequency for this variant is above the maximum credible frequency for a cardiac disease-causing variant in this gene based on internally established thresholds (Karczewski et al. Nature. 2020 May;581(7809):434-443; Whiffin et al. Genet Med. 2017 10;19:1151-1158). Based on the supporting evidence, the association of this alteration with ANK2-related neurodevelopmental disorder is unknown; however, the association with ANK2-related arrhythmia is unlikely. |