Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000048302 | SCV000076315 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1241 of the BRCA1 protein (p.Ser1241Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 16267036). ClinVar contains an entry for this variant (Variation ID: 54979). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000130833 | SCV000185730 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-24 | criteria provided, single submitter | clinical testing | The p.S1241Y variant (also known as c.3722C>A), located in coding exon 9 of the BRCA1 gene, results from a C to A substitution at nucleotide position 3722. The serine at codon 1241 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
Counsyl | RCV000112164 | SCV000489028 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-08-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001719802 | SCV000521141 | likely benign | not provided | 2018-05-03 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 16267036, 15385441, 25722345, 17100994) |
Color Diagnostics, |
RCV000130833 | SCV001340475 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-26 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with tyrosine at codon 1241 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with breast and/or ovarian cancer (PMID: 16267036). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002228165 | SCV002511774 | uncertain significance | not specified | 2022-04-20 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.3722C>A (p.Ser1241Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251278 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3722C>A has been reported in the literature in individual(s) affected with Hereditary Breast And Ovarian Cancer Syndrome (Judkins_2005). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and one ClinVar submitter (evaluation after 2014) cites it as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Sema4, |
RCV000130833 | SCV002538235 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-10 | criteria provided, single submitter | curation | |
University of Washington Department of Laboratory Medicine, |
RCV000130833 | SCV003849951 | 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). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001719802 | SCV004219374 | uncertain significance | not provided | 2023-06-14 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMID: 16267036 (2005)). It has been identified in a study of possible variants which may alter phosphorylation patterns of BRCA1/BRCA2 (PMID: 23704879 (2013)). Additionally, it has also been identified in a study of BRCA1 and BRCA2 regions without essential functions that tolerate variation (PMID: 31911673 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Breast Cancer Information Core |
RCV000112164 | SCV000144850 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing | |
BRCAlab, |
RCV000112164 | SCV004244030 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |