ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.397C>T (p.Arg133Cys) (rs80357457)

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Total submissions: 8
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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) RCV000112474 SCV001161588 benign Breast-ovarian cancer, familial 1 2019-06-18 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 = 3.12E-07
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590742 SCV000699092 uncertain significance not provided 2017-08-14 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.397C>T (p.Arg133Cys) variant (alternatively also known as 516C>T) involves the alteration of a conserved nucleotide. 5/5 in silico tools predict damaging outcome for this variant. This variant was not found in 121408 control chromosomes from ExAC. It is found in gnomAD database at an allele frequency of 0.000014 (4/277094 chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). It has been reported in breast and/or ovarian cancer patients in literature (Judkins_2005, Brooks_2006, Palma_2008) and a clinical database (BIC) without strong evidence for or against pathogenicity. The publications have classified it as a variant of unknown significance (VUS). In addition, two reputable databases (UMD and BIC) have also classified this variant as a VUS. Taken together, this variant is classified as Variant of Unknown Significance.
Counsyl RCV000112474 SCV000786068 uncertain significance Breast-ovarian cancer, familial 1 2018-02-15 criteria provided, single submitter clinical testing
Color Health, Inc RCV000772037 SCV000905042 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590742 SCV001133573 uncertain significance not provided 2019-06-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000772037 SCV001183205 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-27 criteria provided, single submitter clinical testing The p.R133C variant (also known as c.397C>T), located in coding exon 5 of the BRCA1 gene, results from a C to T substitution at nucleotide position 397. The arginine at codon 133 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ITMI RCV000120267 SCV000084419 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000112474 SCV000145275 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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