ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5291T>C (p.Leu1764Pro) (rs80357281)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509995 SCV000607979 likely pathogenic Hereditary cancer-predisposing syndrome 2018-03-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),Other strong data supporting pathogenic classification,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Breast Cancer Information Core (BIC) (BRCA1) RCV000112604 SCV000145441 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112604 SCV000326250 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112604 SCV000786057 pathogenic Breast-ovarian cancer, familial 1 2018-02-14 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112604 SCV000244395 pathogenic Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 0.99
Integrated Genetics/Laboratory Corporation of America RCV000588744 SCV000699234 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-31 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5291T>C (p.Leu1764Pro) variant located in the BRCT domain (via InterPro) involves the alteration of a conserved nucleotide, which 5/5 in silico tools predict a damaging outcome. Multiple functional studies have been performed that support these predictions. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications and databases. The variant of interest has been indicated to cause fold destabilization. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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