ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4039G>C (p.Val1347Leu) (rs80358653)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570365 SCV000668754 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113264 SCV000146361 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Counsyl RCV000113264 SCV000785689 uncertain significance Breast-ovarian cancer, familial 2 2017-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000520753 SCV000617088 uncertain significance not provided 2017-04-17 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.4039G>C at the cDNA level, p.Val1347Leu (V1347L) at the protein level, and results in the change of a Valine to a Leucine (GTT>CTT). Using alternate nomenclature, this variant would be defined as BRCA2 4267G>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Val1347Leu was not observed in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Valine and Leucine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Val1347Leu occurs at a position that is not conserved and is located in the region of interaction with POLH and RAD51 (Roy 2012, Buisson 2014). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Val1347Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.

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