Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clingen Thrombosis Variant Curation Expert Panel, |
RCV000635206 | SCV005061612 | uncertain significance | Hereditary antithrombin deficiency | 2023-09-21 | reviewed by expert panel | curation | The c.529C>T (p.Arg177Cys) variant is reported at a POPMAX FAF of 0.001545 in the African/African American population in gnomAD v3.1.2, and is >BS1 cut-off of 0.0002. One proband in PMID: 28300866 and three probands from internal data with AT deficiency are noted to carry the variant ; however PS4 is not applied since BS1 is met. The variant has a REVEL score of 0.873, which exceeds the cutoff (>0.6) set by the VCEP. Thrombosis VCEP considers this variant as a variant of uncertain significance due to the presence of at least 4 cases with AT deficiency and a high REVEL score. While the population frequency is high, the absence of homozygotes in the population may argue against the variant being benign. The experimental evidence is unreliable with varying activity levels on different assays. A conservative approach would be to classify this variant as uncertain. In summary, based on the evidence available at this time, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BS1, PP3. |
| Labcorp Genetics |
RCV000635206 | SCV000756589 | likely benign | Hereditary antithrombin deficiency | 2024-11-08 | criteria provided, single submitter | clinical testing | |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV003387522 | SCV004099005 | uncertain significance | not provided | 2023-08-02 | criteria provided, single submitter | clinical testing | PP3 |