Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000163234 | SCV000213759 | likely benign | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Gene |
RCV000235446 | SCV000293971 | uncertain significance | not provided | 2017-02-09 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.4931A>G at the cDNA level, p.Glu1644Gly (E1644G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). Using alternate nomenclature, this variant would be defined as BRCA1 5050A>G. A transcriptional assay in yeast and mammalian cells found that this variant demonstrated transcription activation levels similar to wild type (Carvalho 2007). BRCA1 Glu1644Gly 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 Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1644Gly occurs at a position that is not conserved and is located within the BRCT1 domain and a region known to interact with multiple other proteins (Paul 2014, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Glu1644Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Color Diagnostics, |
RCV000163234 | SCV000909004 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-09 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001454137 | SCV001657849 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-08-07 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000112422 | SCV000145209 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-03-30 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000112422 | SCV001238677 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |