Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000775187 | SCV000909405 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-16 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000775187 | SCV001187337 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-04 | criteria provided, single submitter | clinical testing | The p.R213G variant (also known as c.637A>G), located in coding exon 8 of the BRCA1 gene, results from an A to G substitution at nucleotide position 637. The arginine at codon 213 is replaced by glycine, 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. |
| Invitae | RCV001369788 | SCV001566237 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-01-24 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual the Breast Cancer Information Core database (PMID: 10923033). In that individual a pathogenic allele was also identified in BRCA2 which suggests that this c.637A>G variant was not the primary cause of disease.  This variant was also reported in an individual who underwent genetic testing for BRCA1 (PMID: 15235020). ClinVar contains an entry for this variant (Variation ID: 55652). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 213 of the BRCA1 protein (p.Arg213Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. |
| Breast Cancer Information Core |
RCV000112755 | SCV000145644 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing |