Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000471250 | SCV000551035 | uncertain significance | Hereditary antithrombin deficiency | 2016-07-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 269 of the SERPINC1 protein (p.Glu269Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs758087836, ExAC 0.003%). This variant has been reported in a 37 year old male with cerebellar venous infarct, deep vein thrombosis, and pulmonary emboli and recovered following treatment with antithrombin III (AT-III) concentrate. Family studies showed that this variant segregated in three individuals with reduced concentrations of AT-III plus venous thromboembolism (VTE), one individual with reduced AT-III concentrations but no VTE, and an unaffected 17 year old female family member (PMID: 1430264). This variant is also known as 237 Glu to Lys or Truro variant in the literature. Experimental studies have shown that this missense change alters heparin pentasaccharide affinity and binding kinetics in vitro suggesting that this amino acid residue is important for protein function (PMID: 10966821, 16973611). In summary, this missense change has been reported to alter binding to heparin in vitro and segregates in a family with history of venous thromboembolism. However, this variant is also present in population databases and without additional functional and/or genetic data, this change has been classified as a Variant of Uncertain Significance. |
Mayo Clinic Laboratories, |
RCV003480641 | SCV004226418 | likely pathogenic | not provided | 2022-12-30 | criteria provided, single submitter | clinical testing | PP1, PM1, PM2, PS4_supporting |