ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2579T>C (p.Leu860Pro) (rs587780242)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212328 SCV000150055 uncertain significance not provided 2017-05-16 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2579T>C at the cDNA level, p.Leu860Pro (L860P) at the protein level, and results in the change of a Leucine to a Proline (CTT>CCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Leu860Pro was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Leucine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. BRIP1 Leu860Pro occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRIP1 Leu860Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000116146 SCV000213546 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000196126 SCV000255156 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-30 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 860 of the BRIP1 protein (p.Leu860Pro). 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 not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 128177). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C25"). 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.
Color RCV000116146 SCV000684224 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000662554 SCV000785137 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-05-16 criteria provided, single submitter clinical testing

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