ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1780A>C (p.Ile594Leu) (rs431825287)

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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 RCV000167234 SCV000218071 uncertain significance Hereditary cancer-predisposing syndrome 2015-12-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (benign)
GeneDx RCV000219220 SCV000279350 uncertain significance not provided 2016-01-25 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1780A>C at the cDNA level, p.Ile594Leu (I594L) at the protein level, and results in the change of an Isoleucine to a Leucine (ATA>CTA). Using alternate nomenclature, this variant would be defined as BRCA2 2008A>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ile594Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Isoleucine and Leucine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ile594Leu occurs at a position where amino acids with properties similar to Isoleucine are tolerated across species and is not located in a known functional domain (Borg 2010, UniProt). 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 Ile594Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000082892 SCV000743262 uncertain significance Breast-ovarian cancer, familial 2 2014-10-08 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082892 SCV000114966 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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