Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236530 | SCV000293217 | uncertain significance | not provided | 2016-09-27 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.32T>G at the cDNA level, p.Val11Gly (V11G) at the protein level, and results in the change of a Valine to a Glycine (GTA>GGA). Using alternate nomenclature, this variant would be defined as BRCA1 151T>G. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRCA1 Val11Gly 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 Valine and Glycine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Val11Gly occurs at a position that is conserved through mammals and is located in the RING domain and the regions of interaction with BRD7 and BARD1 (Narod 2004, Borg 2010, Harte 2010, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Val11Gly is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000509835 | SCV000608110 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-01-26 | criteria provided, single submitter | clinical testing | The p.V11G variant (also known as c.32T>G), located in coding exon 1 of the BRCA1 gene, results from a T to G substitution at nucleotide position 32. The valine at codon 11 is replaced by glycine, an amino acid with dissimilar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay. (Findlay GM et al. Nature, 2018 10;562:217-222). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Invitae | RCV000792051 | SCV000931323 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 11 of the BRCA1 protein (p.Val11Gly). 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 performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 245973). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Brotman Baty Institute, |
RCV001072350 | SCV001237715 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |