ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.1456T>C (p.Phe486Leu) (rs55906931)

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Total submissions: 21
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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) RCV000111622 SCV000244302 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 = 0.00000000000186
Invitae RCV000167847 SCV000075495 benign Hereditary breast and ovarian cancer syndrome 2018-01-05 criteria provided, single submitter clinical testing
Counsyl RCV000111622 SCV000154030 likely benign Breast-ovarian cancer, familial 1 2014-03-31 criteria provided, single submitter literature only
GeneDx RCV000120299 SCV000167241 benign not specified 2014-01-22 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 RCV000162618 SCV000213050 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000111622 SCV000267692 benign Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000167847 SCV000297222 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-09-02 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120299 SCV000333420 likely benign not specified 2015-08-04 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000111622 SCV000575698 likely benign Breast-ovarian cancer, familial 1 2015-09-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120299 SCV000591333 benign not specified 2012-11-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120299 SCV000600251 likely benign not specified 2017-06-08 criteria provided, single submitter clinical testing
Color RCV000162618 SCV000682962 likely benign Hereditary cancer-predisposing syndrome 2014-12-15 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000111622 SCV000746297 uncertain significance Breast-ovarian cancer, familial 1 2017-12-03 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000656642 SCV000806895 likely benign not provided 2017-05-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000120299 SCV000916795 benign not specified 2018-08-21 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1456T>C (p.Phe486Leu) 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 0.00028 in 278056 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (0.00028 vs 0.001), allowing no conclusion about variant significance. This variant has been reported in cis with Y179C and N550H in most patients and has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer; however a possible lack of cosegregation in at least two families has been reported (Caligo_2009; Mahfoudh_2012). Co-occurrences with other pathogenic variants have been reported (BRCA1 p.W321X; BRCA2 p.S1970X; BRCA2 p.E2028KfsX19), providing supporting evidence for a benign role. Several publications report experimental evidence evaluating an impact on protein function, including homologous repair, protein-protein interactions, and single stand annealing assays, all of which showed no damaging effect caused by the variant (Caligo_2009; Anantha_2017). Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments; however, the majority of labs classified the variant in the benign spectrum (LB/B = 8; VUS = 2). Based on the evidence outlined above, the variant was classified as benign.
ITMI RCV000120299 SCV000084451 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000111622 SCV000144101 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000111622 SCV000189326 benign Breast-ovarian cancer, familial 1 2011-02-25 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000111622 SCV000733658 benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656642 SCV000778769 likely benign not provided 2017-08-02 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162618 SCV000805227 likely benign Hereditary cancer-predisposing syndrome 2018-04-05 no assertion criteria provided clinical testing

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