ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2252T>C (p.Met751Thr) (rs587781684)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129847 SCV000184664 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-08 criteria provided, single submitter clinical testing The p.M751T variant (also known as c.2252T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 2252. The methionine at codon 751 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001083025 SCV000549288 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759501 SCV000888859 uncertain significance not provided 2018-03-16 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129847 SCV000909349 likely benign Hereditary cancer-predisposing syndrome 2017-10-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780974 SCV000918684 uncertain significance not specified 2017-10-26 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2252T>C (p.Met751Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide located outside of any known functional domain or repeat. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index), however no functional studies supporting these predictions were published at the time of this evaluation. This variant was found in 1/245988 control chromosomes (gnomAD) at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005), suggesting that it is not a common polymorphism. The variant has been reported in one HBOC individual (Judkins_2005), without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
Sharing Clinical Reports Project (SCRP) RCV000239259 SCV000297591 benign Breast-ovarian cancer, familial 1 2010-09-08 no assertion criteria provided clinical testing

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