title: Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea.
abstract: OBJECTIVE
  We describe a rationale for the re-classification of the BRCA1 c.5539T>C (L1780P) variant using a clinical evidence.
  
  
  METHODS
  A retrospective review was conducted to identify all patients with breast or ovarian cancer and the L1780P variant between 2002 and 2015 at a single institution.
  
  
  RESULTS
  We identified the BRCA1/2 genetic mutation test results of 1223 breast cancer patients and 174 patients with ovarian cancer. Of the 160 BRCA 1/2 variant unknown significance, 16 (10.0%) patients were identified as having the L1780P variant. Among them, 10 had breast cancer, 4 had ovarian cancer, and 2 had both breast and ovarian cancer. Thirteen (81.3%) patients with this variant had family histories of breast or ovarian cancer. Two (16.7%) also had comorbid ovarian cancer. Two patients with this variant showed that co-segregation of the disease in multiple family members and family histories of breast and ovarian cancer. This variant was found to be either absent or at extremely low frequency in general population databases.
  
  
  CONCLUSIONS
  The L1780P variant might confer to "Likely pathogenic" according to a clinical evidence and the ACMG standards and guidelines. A nation-wide or global survey and a functional analysis are needed to confirm the pathogenicity of the L1780P variant.
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jai Min
authors.initials: JM
authors.lastname: Ryu
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Goeun
authors.initials: G
authors.lastname: Kang
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jonghan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Bae
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Sungmin
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hyun-June
authors.initials: HJ
authors.lastname: Paik
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Daerim St. Mary's Hospital, South Korea.
authors.forename: Sung-Shin
authors.initials: SS
authors.lastname: Park
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: jeongeon.lee@samsung.com.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Breast Care Center, Daerim St. Mary's Hospital, South Korea. Electronic address: brcakorea@gmail.com.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D056910:Republic of Korea; D012189:Retrospective Studies
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA1; Breast neoplasm; Missense mutation; Ovarian neoplasm