Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clingen Thrombosis Variant Curation Expert Panel, |
RCV000019658 | SCV004037394 | pathogenic | Hereditary antithrombin deficiency | 2023-09-21 | reviewed by expert panel | curation | The NM_000488.4(SERPINC1):c.655A>G (p.Asn219Asp) missense variant is reported at a Popmax FAF of 0.00000488 (non-Finnish European) in gnomAD v3.1.2 and a frequency of 0.000008792 (1/113744) in gnomAD v2.1.1, meeting criteria for PM2_Supporting. It has a REVEL score of 0.898 (PP3 is >0.6). One proband from PMID: 28300866 (family of four affected individuals), 2 probands from PMID: 15630491, 1 proband from PMID: 7989582, and 1 proband from PMID: 7795154 meet phenotype criteria for PS4, PP4 and PP1_Strong. Of note, PMID: 30005274 reports that the Asn219Asp variant associated with Type II RS is hardly detected by the different anti-FXa or anti-FIIa assay methods. In summary, the variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PS4, PP1_Strong, PP3, PP4, PM2_Supporting. |
Institute for Genomic Medicine |
RCV000019658 | SCV001423681 | likely pathogenic | Hereditary antithrombin deficiency | 2017-10-01 | criteria provided, single submitter | clinical testing | [ACMG/AMP: PM2, PM5, PS4_Moderate, PP2, PP3] This alteration is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], has previously been observed in multiple unrelated patients with the same phenotype [PS4_Moderate], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3]. |
Genetics and Molecular Pathology, |
RCV000019658 | SCV002556528 | pathogenic | Hereditary antithrombin deficiency | 2020-06-10 | criteria provided, single submitter | clinical testing | PM2, PM5, PS3, PP5 |
OMIM | RCV000019658 | SCV000039956 | pathogenic | Hereditary antithrombin deficiency | 1994-12-01 | no assertion criteria provided | literature only |