Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000047971 | SCV000075984 | uncertain significance | Hereditary breast and ovarian cancer syndrome | 2018-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 933 of the BRCA1 protein (p.Gly933Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 37490). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Gene |
RCV000256124 | SCV000321423 | uncertain significance | not provided | 2016-05-20 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.2798G>A at the cDNA level, p.Gly933Asp (G933D) at the protein level, and results in the change of a Glycine to an Aspartic Acid (GGT>GAT). Using alternate nomenclature, this variant would be defined as BRCA1 2917G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gly933Asp was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glycine and Aspartic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Gly933Asp occurs at a position that is not conserved and is located in the DNA binding domain and in the region of interaction with RAD51 (Chen 1998, Narod 2004). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA1 Gly933Asp is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Ambry Genetics | RCV000561212 | SCV000660982 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-10-18 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence |
| Color | RCV000561212 | SCV000683062 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-12 | criteria provided, single submitter | clinical testing | |
| Sharing Clinical Reports Project |
RCV000031071 | SCV000053667 | uncertain significance | Breast-ovarian cancer, familial 1 | 2012-04-26 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000031071 | SCV000144548 | uncertain significance | Breast-ovarian cancer, familial 1 | 2004-11-25 | no assertion criteria provided | clinical testing |