ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3600G>C (p.Gln1200His) (rs56214134)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000167802 SCV000076259 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000120295 SCV000167293 benign not specified 2014-02-05 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000112129 SCV000195923 benign Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162833 SCV000213319 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000112129 SCV000220665 likely benign Breast-ovarian cancer, familial 1 2014-09-03 criteria provided, single submitter literature only
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000167802 SCV000576440 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120295 SCV000593673 likely benign not specified 2017-05-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282578 SCV000602690 benign none provided 2020-04-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162833 SCV000683114 likely benign Hereditary cancer-predisposing syndrome 2015-11-17 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120295 SCV000806936 benign not specified 2017-04-25 criteria provided, single submitter clinical testing
ITMI RCV000120295 SCV000084447 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000112129 SCV000144802 benign Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353562 SCV000591454 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Gln1200His variant was identified in at least 11 of 122840 proband chromosomes (frequency 0.005) from individuals or families with breast cancer, ovarian cancer or prostate cancer, and was identified in 1 of 2892 control chromosomes (frequency: 0.0003) (Anczukow 2008, Capanu 2011, Caux-Moncoutier 2011, Judkins 2005, Lee 2008, McKean-Cowdin 2005, Newman 1998, Osorio 2007, Zuhlke 2004). The variant was also identified in the HGMD, UMD (7X as a neutral variant), and the BIC database (17X with no clinical importance). The variant was listed in UMD with a co-occurring pathogenic mutation in BRCA1 (c.5041insATTA (p.Thr1681IlefsX3)), and Judkins (2005) also identified the variant in trans with a pathogenic BRCA1 mutation (BRCA1 4730insG), increasing the likelihood that this variant does not have clinical importance. The variant was listed in dbSNP (ID: rs56214134) with a minor allele frequency of 0.001 (1000 Genomes Project), and in the NHLBI Exome Sequencing Project with a frequency of 0.003 in African American alleles, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. This residue is not conserved in mammals and lower organisms and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. A functional study by Anczukow (2008) did not detect an effect of the variant on intron 11 splicing efficiency. In addition, two in silico studies using multifactorial likelihood ratio models suggest that this is likely a neutral variant (Lindor 2012, Osorio 2007). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735466 SCV000863603 benign Breast and/or ovarian cancer 2013-11-04 no assertion criteria provided clinical testing

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