ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3649T>C (p.Ser1217Pro) (rs273900712)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164401 SCV000215037 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000112145 SCV000144823 uncertain significance Breast-ovarian cancer, familial 1 2010-12-17 no assertion criteria provided clinical testing
Color RCV000164401 SCV000683120 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Counsyl RCV000112145 SCV000488309 uncertain significance Breast-ovarian cancer, familial 1 2016-02-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765362 SCV000896627 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000758816 SCV000292516 uncertain significance not provided 2018-10-15 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3649T>C at the cDNA level, p.Ser1217Pro (S1217P) at the protein level, and results in the change of a Serine to a Proline (TCT>CCT). Also reported as BRCA1 3768T>C using alternate nomenclature, this variant has been observed in individuals with breast, ovarian, and/or pancreatic cancer (Sugano 2008, Axilbund 2009, Stegel 2011, Zhen 2015, Azzollini 2016, Wen 2018). This variant has been reported to abolish local CK2A1 and CSNK2A1 binding, preventing phosphorylation of this residue in in vivo studies; however the biological significance of this is not known (Tram 2013). BRCA1 Ser1217Pro was observed at an allele frequency of 0.05% (12/25,792) in individuals of Finnish ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Ser1217Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000048271 SCV000076284 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 1217 of the BRCA1 protein (p.Ser1217Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs273900712, ExAC 0.02%). This variant has been reported in individuals affected with breast and/or ovarian cancer, and pancreatic cancer (PMID: 19016756, 21232165, 27062684, 19029836, 25356972). This variant is also known as 3768T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 54953). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758816 SCV000887673 uncertain significance not provided 2018-06-06 criteria provided, single submitter clinical testing

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