Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Myriad Genetics, |
RCV001075917 | SCV004018695 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-06-28 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 30209399, 35196514]. |
| Ambry Genetics | RCV004031192 | SCV005025865 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-22 | criteria provided, single submitter | clinical testing | The p.Q1747P variant (also known as c.5240A>C), located in coding exon 18 of the BRCA1 gene, results from an A to C substitution at nucleotide position 5240. The glutamine at codon 1747 is replaced by proline, an amino acid with similar 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 Oct;562:217-222). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Brotman Baty Institute, |
RCV001075917 | SCV001241573 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro | ||
| Prevention |
RCV004731089 | SCV005335581 | uncertain significance | BRCA1-related disorder | 2024-07-15 | no assertion criteria provided | clinical testing | The BRCA1 c.5240A>C variant is predicted to result in the amino acid substitution p.Gln1747Pro. To our knowledge, this variant has not been reported in the literature in individuals with hereditary cancer or in a large population database, indicating this variant is rare. Functional studies indicate this variant impacts protein function (Adamovich AI et al. 2022. PubMed ID: 35196514; Findlay GM et al. 2018. PubMed ID: 30209399). This variant has conflicting interpretations in ClinVar from likely pathogenic to a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/867266/). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |