ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1040T>C (p.Leu347Pro) (rs786201819)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164304 SCV000214935 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000164304 SCV000911794 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-09 criteria provided, single submitter clinical testing
Counsyl RCV000409937 SCV000489953 uncertain significance Fanconi anemia, complementation group J 2016-08-22 criteria provided, single submitter clinical testing
Counsyl RCV000410942 SCV000489954 uncertain significance Neoplasm of ovary 2016-08-22 criteria provided, single submitter clinical testing
GeneDx RCV000371659 SCV000329154 uncertain significance not provided 2018-10-01 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1040T>C at the cDNA level, p.Leu347Pro (L347P) at the protein level, and results in the change of a Leucine to a Proline (CTA>CCA). This variant has been observed in at least one individual with triple negative breast cancer unselected for family history and has also been reported in healthy control subjects (Couch 2015, Ramus 2015, Weber-Lassalle 2018). BRIP1 Leu347Pro was not observed 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 BRIP1 Leu347Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000636110 SCV000757542 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 347 of the BRIP1 protein (p.Leu347Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 25452441). ClinVar contains an entry for this variant (Variation ID: 184958). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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