ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.655T>C (p.Cys219Arg) (rs730881630)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160331 SCV000210834 uncertain significance not provided 2018-07-11 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.655T>C at the cDNA level and p.Cys219Arg (C219R) at the protein level, and results in the change of a Cysteine to an Arginine (TGT>CGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRIP1 Cys219Arg was not observed at a significant allele frequency 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 Cys219Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000214329 SCV000277179 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-20 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000228414 SCV000291055 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 219 of the BRIP1 protein (p.Cys219Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. 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: 182341). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Counsyl RCV000410746 SCV000490077 uncertain significance Fanconi anemia, complementation group J 2016-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000412358 SCV000490078 uncertain significance Neoplasm of ovary 2016-10-31 criteria provided, single submitter clinical testing
Color RCV000214329 SCV000689410 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-24 criteria provided, single submitter clinical testing

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