ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3327A>C (p.Lys1109Asn) (rs41293449)

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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) RCV000031103 SCV000244339 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 = 0.0000307
Ambry Genetics RCV000162723 SCV000213185 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.
Invitae RCV000205796 SCV000261249 benign Hereditary breast and ovarian cancer syndrome 2020-11-21 criteria provided, single submitter clinical testing
Counsyl RCV000031103 SCV000488284 benign Breast-ovarian cancer, familial 1 2016-02-12 criteria provided, single submitter clinical testing
GeneDx RCV000432399 SCV000512300 likely benign not specified 2017-03-03 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586144 SCV000699012 likely benign not provided 2016-02-11 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162723 SCV000903026 benign Hereditary cancer-predisposing syndrome 2016-04-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031103 SCV000053699 benign Breast-ovarian cancer, familial 1 2010-11-30 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000586144 SCV000591436 uncertain significance not provided no assertion criteria provided clinical testing The c.3327A>C / p.Lys1109Asn is a missense variant, located in exon 11 of BRCA1. It is listed in dbSNP database (rs-id=rs41293449) from a clinical source where no frequency information was provided; therefore no conclusions can be drawn for its population occurrence. The c.3327A_C variant is classified as “not pathogenic or of no clinical significance” by two studies (Easton_2007_17924331, Tavtigian_2008_18951461. Another variant in the same position and resulting in the same amino acid alteration (c.3327A>G, p.lys1109Asn) is also reported in LOVD and BIC databases with unknown pathogenicity. A variant classification study using in silico and probability based likelyhood pathogenicity assays also presents this variant to have an unclassified pathogenicity (Spurdle_2008_18375895, Lindor_2011_21990134). The Lys1109 residue is conserved across mammals and species and computational analyses, SIFT, suggest that this variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. Based on the above information, the pathogenicity of this variants cannot be determined, thus we tend to classify it as a variant of uncertain clinical significance (VUS).

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