Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Hum Mutat. 2010 Nov;31(11):1205-15. doi: 10.1002/humu.21343.
The MUTYH gene encodes a DNA glycosylase involved in base excision repair (BER). Biallelic pathogenic MUTYH variants have been associated with colorectal polyposis and cancer. The pathogenicity of a few variants is beyond doubt, including c.536A4G/p.Tyr179Cys and c.1187G4A/p.Gly396Asp (previously c.494A4G/p.Tyr165Cys and c.1145G4A/p.Gly382Asp).However, for a substantial fraction of the detected variants, the clinical significance remains uncertain,compromising molecular diagnostics and thereby genetic counseling. We have established an interactive MUTYH gene sequence variant database (www.lovd.nl/MUTYH) with the aim of collecting and sharing MUTYH genotype and phenotype data worldwide. To support standard variant description, we chose NM_001128425.1 as the reference sequence. The database includes records with variants per individual, linked to available phenotype and geographic origin data as well as records with in vitro functional and in silico test data. As of April 2010, the database contains 1968 published and 423 unpublished submitted entries, and 230 and 61 unique variants,respectively. This open-access repository allows all involved to quickly share all variants encountered and communicate potential consequences, which will be especially useful to classify variants of uncertain significance.
MUTYH 基因编码一种参与碱基切除修复 (BER) 的 DNA 糖苷酶。双等位致病性 MUTYH 变体与结直肠息肉病和癌症有关。一些变体的致病性是毫无疑问的，包括 c.536A4G/p.Tyr179Cys 和 c.1187G4A/p.Gly396Asp（以前称为 c.494A4G/p.Tyr165Cys 和 c.1145G4A/p.Gly382Asp）。然而，对于检测到的大量变体，其临床意义仍不确定，这影响了分子诊断和遗传咨询。我们建立了一个互动的 MUTYH 基因序列变体数据库（www.lovd.nl/MUTYH），旨在收集和分享全球范围内的 MUTYH 基因型和表型数据。为了支持标准变体描述，我们选择 NM_001128425.1 作为参考序列。该数据库包含每个个体的变体记录，与可用的表型和地理起源数据以及体外功能和计算机模拟测试数据相关联。截至 2010 年 4 月，该数据库包含 1968 个已发表和 423 个未发表的提交条目，分别有 230 个和 61 个独特变体。这个开放获取的存储库允许所有相关人员快速共享遇到的所有变体，并交流潜在的后果，这对于分类不确定意义的变体将特别有用。
