Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112009 | SCV001161501 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-06-18 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000314 |
Gene |
RCV000590820 | SCV000210142 | uncertain significance | not provided | 2015-08-04 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.3143G>T at the cDNA level, p.Gly1048Val (G1048V) at the protein level, and results in the change of a Glycine to a Valine (GGT>GTT). Using alternate nomenclature, this variant would be defined as BRCA1 3262G>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gly1048Val 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 Valine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Gly1048Val occurs at a position that is not conserved and is located within the DNA-binding domain and the region of interaction with RAD51 and BASC (UniProt). 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 Gly1048Val is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000214911 | SCV000277268 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-11 | criteria provided, single submitter | clinical testing | The p.G1048V variant (also known as c.3143G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3143. The glycine at codon 1048 is replaced by valine, 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. |
Color Diagnostics, |
RCV000214911 | SCV000683087 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-26 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 1048 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. A multifactorial analysis has reported co-occurrence and family history likelihood ratios of 1.1391 and 0.0135, respectively (PMID: 31131967). This variant has been identified in 1/251002 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may not be associated with disease, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590820 | SCV000699006 | uncertain significance | not provided | 2016-02-01 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000590820 | SCV002049680 | likely benign | not provided | 2021-10-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002514243 | SCV003242288 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-20 | criteria provided, single submitter | clinical testing | |
Breast Cancer Information Core |
RCV000112009 | SCV000144649 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |