Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clingen Thrombosis Variant Curation Expert Panel, |
RCV000019646 | SCV005367710 | pathogenic | Hereditary antithrombin deficiency | 2024-07-03 | reviewed by expert panel | curation | The c.482G>A (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 161 (p.Arg161Gln also known as ATIII Geneva). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008790 (1/113762 alleles) in the European population, which is lower than the ClinGen SERPINC1 threshold ([<0.00002]) for PM2, and therefore meets this criterion (PM2_supporting). The computational predictor REVEL gives a score of 0.691, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function, meeting criteria for PP3. The variant has been reported in at least 9 probands with AT deficiency in the literature (9 points applied PMID 28300866, PMID 2229057, PMID 3603409). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PM2_supporting, PP3, PS4_very strong. |
OMIM | RCV000019646 | SCV000039944 | pathogenic | Hereditary antithrombin deficiency | 1990-11-05 | no assertion criteria provided | literature only | |
CSER _CC_NCGL, |
RCV000019646 | SCV000190630 | uncertain significance | Hereditary antithrombin deficiency | 2014-06-01 | no assertion criteria provided | research | |
ISTH- |
RCV000019646 | SCV002515493 | pathogenic | Hereditary antithrombin deficiency | no assertion criteria provided | clinical testing |