ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4081A>C (p.Met1361Leu) (rs80357218)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112244 SCV000244353 benign 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 1 based on posterior probability = 0.000196
Invitae RCV000048437 SCV000076450 likely benign Hereditary breast and ovarian cancer syndrome 2017-09-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162982 SCV000213470 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Counsyl RCV000112244 SCV000487985 benign Breast-ovarian cancer, familial 1 2015-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000438101 SCV000521417 likely benign not specified 2017-07-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000162982 SCV000688464 likely benign Hereditary cancer-predisposing syndrome 2017-07-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000438101 SCV000699106 likely benign not specified 2019-04-09 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4081A>C (p.Met1361Leu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 245718 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4081A>C has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Lee_2008). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Two studies using multifactorial likelihood models have classified this variant as having a neutral impact (Easton_2007, Lindor_2012) (IARC class I). To our knowledge, no other experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories and one expert panel have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign and the expert panel has classified the variant as Benign. Based on the evidence outlined above, the variant was classified as likely benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112244 SCV000144960 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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