Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000132050 | SCV000187112 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-03-04 | criteria provided, single submitter | clinical testing | The p.P1469S variant (also known as c.4405C>T or4524C>T), located in coding exon 12 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4405. The proline at codon 1469 is replaced by serine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs80356960.This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be benign and deleterious by PolyPhen and SIFT in silico analyses, respectively.Since supporting evidence is limited at this time, the clinical significance ofp.P1469Sremains unclear. |
Color Diagnostics, |
RCV000132050 | SCV001348227 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-08 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 1469 of the BRCA1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. This variant has been observed in an individual affected with breast cancer (PMID 12491499). To our knowledge, functional assays have not been performed for this variant. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Breast Cancer Information Core |
RCV000112334 | SCV000145086 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing |