BACKGROUND Inherited deficiency of the antithrombin (hereditary antithrombin deficiency, AT deficiency, OMIM #613118) is a relatively rare (1:2000-3000) autosomal-dominant disorder with high risk of venous thromboembolism. Mutations in the serpin family C member 1 gene (SERPINC1) can lead to Quantitative (type I) and Qualitative (type II) types of antithrombin deficiency. We describe a new genetic variant in the SERPINC1 gene and our approach to variant interpretation. CASE PRESENTATION We observed a 29 y.o. female proband with the episode of venous thrombosis at the age of 18 and family history of thrombosis. The antithrombin level in our patient was low, 44-48% (AT deficiency type I). A new genetic variant c.662G > C (p.W221S) in the SERPINC1 gene was detected in proband and affected father but was absent in healthy sister. We used in silico tools to evaluate the possible impact of p.W221S variant on protein structure and function. In mutated SERPINC1 protein a new N-linked glycosylation site is formed, however, it is unclear if the glycosylation at 219-221 site is possible. CONCLUSION The proband was provided with appropriate genetic counseling and referred to a hematologist. Based on all the evidence we classify the p.W221S variant as variant of unknown clinical significance. In this paper we discuss some aspects of genetic counseling, variant interpretation and thromboembolic prophilaxis.

中文翻译：

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SERPINC1 基因中的新遗传变异：遗传性抗凝血酶缺乏病例报告、家族性血栓形成和遗传咨询的注意事项。

背景 遗传性抗凝血酶缺乏症（遗传性抗凝血酶缺乏症，AT 缺乏症，OMIM #613118）是一种相对罕见（1:2000-3000）的常染色体显性遗传性疾病，具有较高的静脉血栓栓塞风险。丝氨酸蛋白酶抑制剂家族 C 成员 1 基因 (SERPINC1) 的突变可导致定量（I 型）和定性（II 型）类型的抗凝血酶缺乏。我们描述了 SERPINC1 基因中的一个新的遗传变异以及我们的变异解释方法。病例介绍 我们观察了一名 29 岁女性先证者，她在 18 岁时出现静脉血栓形成，并且有血栓形成家族史。该患者的抗凝血酶水平较低，为 44-48%（AT 缺陷 I 型）。在先证者和受影响的父亲中检测到 SERPINC1 基因中的新遗传变异 c.662G > C (p.W221S)，但在健康姐妹中不存在。我们使用计算机工具来评估 p.W221S 变体对蛋白质结构和功能的可能影响。在突变的 SERPINC1 蛋白中，形成了一个新的 N 连接糖基化位点，然而，尚不清楚 219-221 位点的糖基化是否可能。结论 先证者接受了适当的遗传咨询并转诊至血液科医生。根据所有证据，我们将 p.W221S 变异分类为临床意义未知的变异。在本文中，我们讨论遗传咨询、变异解释和血栓栓塞预防的一些方面。