Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000170698 | SCV000223251 | uncertain significance | not provided | 2024-05-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
| Labcorp Genetics |
RCV000467208 | SCV000545140 | likely benign | Long QT syndrome | 2024-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000619169 | SCV000738243 | likely benign | Cardiovascular phenotype | 2022-02-24 | 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, |
RCV001175061 | SCV001338608 | likely benign | not specified | 2020-04-27 | criteria provided, single submitter | clinical testing | Variant summary: ANK2 c.3931G>A (p.Val1311Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251292 control chromosomes. The observed variant frequency is approximately 6.4- fold the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3931G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |