Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000658344 | SCV000780116 | uncertain significance | not provided | 2018-05-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ANK2 gene. The H2950Y variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 2/18836 (0.01%) alleles from individuals of East Asian ancestry in large population cohorts (Lek et al., 2016). The H2950Y 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, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Illumina Laboratory Services, |
RCV001150057 | SCV001311065 | 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. |
| Ambry Genetics | RCV004629280 | SCV005132039 | uncertain significance | Cardiovascular phenotype | 2024-05-05 | criteria provided, single submitter | clinical testing | The p.H2950Y variant (also known as c.8848C>T), located in coding exon 38 of the ANK2 gene, results from a C to T substitution at nucleotide position 8848. The histidine at codon 2950 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |