ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1817C>T (p.Pro606Leu) (rs80358469)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163125 SCV000213637 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077268 SCV000145956 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000163125 SCV000911865 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing
Counsyl RCV000077268 SCV000786519 uncertain significance Breast-ovarian cancer, familial 2 2018-05-17 criteria provided, single submitter clinical testing
GeneDx RCV000479578 SCV000569878 uncertain significance not provided 2017-02-22 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1817C>T at the cDNA level, p.Pro606Leu (P606L) at the protein level, and results in the change of a Proline to a Leucine (CCG>CTG). Using alternate nomenclature, this variant would be defined as BRCA2 2045C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Pro606Leu occurs at a position that is not covered in the NHLBI Exome Sequencing Project. Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Pro606Leu occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Pro606Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000779988 SCV000916970 uncertain significance not specified 2017-12-21 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1817C>T (p.Pro606Leu) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 235704 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. BIC cites the variant in a patient with co-occurrence of a pathogenic BRCA2 variant c.1819A>T/p.Lys607Ter, suggesting the variant of interest likely is not the cause of disease. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance - possibly normal variant until additional information becomes available.
Invitae RCV000043900 SCV000071913 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077268 SCV000109065 uncertain significance Breast-ovarian cancer, familial 2 2009-12-23 no assertion criteria provided clinical testing

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