Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486788 | SCV000566325 | uncertain significance | not provided | 2016-10-07 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.993G>C at the cDNA level, p.Arg331Ser (R331S) at the protein level, and results in the change of an Arginine to a Serine (AGG>AGC). This variant, also published as BRCA1 1112G>C using alternate nomenclature, has been observed in at least two individuals of Slovenian ancestry from families with breast and/or ovarian cancer (Stegel 2011). BRCA1 Arg331Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Serine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Arg331Ser occurs at a position that is not conserved and is located in DNA binding domain and region of interaction with multiple proteins (Narod 2004, Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Arg331Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Color Diagnostics, |
RCV000775181 | SCV000909392 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001340979 | SCV001534815 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-24 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 55774). This missense change has been observed in individual(s) with personal and/or family history of breast and/or ovarian cancer (PMID: 21232165). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 331 of the BRCA1 protein (p.Arg331Ser). |
University of Washington Department of Laboratory Medicine, |
RCV000775181 | SCV003846246 | 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). |
Breast Cancer Information Core |
RCV000111523 | SCV000143974 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing |