ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1001C>T (p.Pro334Leu) (rs41286290)

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Total submissions: 9
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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) RCV000111527 SCV000244292 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 = 0.000000271
Invitae RCV001083751 SCV000075319 benign Hereditary breast and ovarian cancer syndrome 2020-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000254634 SCV000209918 likely benign not specified 2017-10-04 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.
Ambry Genetics RCV000162971 SCV000213459 benign Hereditary cancer-predisposing syndrome 2019-05-22 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587332 SCV000698824 benign not provided 2017-04-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1001C>T (p.Pro334Leu) variant involves the alteration of a non-conserved nucleotide and is predicted to be damaging by 3/5 in silico tools. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. Functional studies show the variant to not affect splicing (Anczukow_2008, Caux-Moncoutier_2009). This variant was found in 2/121404 control chromosomes from ExAC at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005); however, it could still be a rare polymorphism. The variant has been reported in multiple affected individuals via publications and databases, including co-occurrence with other BRCA1 pathogenic variants in other allele (in trans), 2120insA (Judkins_2005), c.66_67delAG (BIC), and an unspecified deleterious variant (Spearman_2008), strongly supporting for benign outcome. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign. Taken together, this variant is classified as Benign.
Counsyl RCV000111527 SCV000784954 likely benign Breast-ovarian cancer, familial 1 2017-02-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162971 SCV000902889 benign Hereditary cancer-predisposing syndrome 2016-06-13 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000587332 SCV001501182 likely benign not provided 2020-07-01 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111527 SCV000143978 benign Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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