Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129847 | SCV000184664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-30 | 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 variant was reported in 0/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med, 2021 02;384:428-439). 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 ovarian cancer syndrome | 2023-11-15 | 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 Diagnostics, |
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, |
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. |
University of Washington Department of Laboratory Medicine, |
RCV000129847 | SCV003847812 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
Sharing Clinical Reports Project |
RCV000239259 | SCV000297591 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-09-08 | no assertion criteria provided | clinical testing |