ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1036C>T (p.Pro346Ser) (rs80357015)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195311 SCV000075328 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130509 SCV000185378 likely benign Hereditary cancer-predisposing syndrome 2017-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign)
GeneDx RCV000047315 SCV000209919 likely benign not specified 2017-05-30 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.
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000047315 SCV000586877 likely benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Counsyl RCV000030970 SCV000785447 uncertain significance Breast-ovarian cancer, familial 1 2017-08-10 criteria provided, single submitter clinical testing
Color RCV000130509 SCV000902944 benign Hereditary cancer-predisposing syndrome 2016-10-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047315 SCV000916714 likely benign not specified 2019-04-12 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1036C>T (p.Pro346Ser) results in a non-conservative amino acid change located in the BRCA1, serine-rich domain of 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 0.00018 in 277056 control chromosomes, predominantly at a frequency of 0.0026 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. The variant, c.1036C>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Kuo_2012, Sun_2014, Thirthagiri_2008, Flower_2015, Chao_2016, Lai_2017, Chan_2018). Thus, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1x VUS, 3x likely benign, 1X benign). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000195311 SCV001133475 benign not provided 2019-03-12 criteria provided, single submitter clinical testing
Mendelics RCV000030970 SCV001140612 benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000030970 SCV000053561 benign Breast-ovarian cancer, familial 1 2012-02-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000030970 SCV000143987 uncertain significance Breast-ovarian cancer, familial 1 2010-09-18 no assertion criteria provided clinical testing

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