Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571448 | SCV000665042 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-07 | criteria provided, single submitter | clinical testing | The p.E1731* pathogenic mutation (also known as c.5191G>T), located in coding exon 17 of the BRCA1 gene, results from a G to T substitution at nucleotide position 5191. This changes the amino acid from a glutamic acid to a stop codon within coding exon 17. 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). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV000698353 | SCV000827013 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 37646). 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). This sequence change creates a premature translational stop signal (p.Glu1731*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). |
| Baylor Genetics | RCV001076151 | SCV004215036 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-08-05 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001076151 | SCV004839571 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-11-13 | criteria provided, single submitter | clinical testing | The c.5191G>T (p.Glu1731*) variant of the BRCA1 gene creates an early stop codon. It is expected to result in an absent or disrupted protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Truncating variants in BRCA1 are known to be pathogenic (PMID: 21989022, 17661172, 22762150). Therefore, the c.5191G>T (p.Glu1731*) variant of the BRCA1 gene is classified as pathogenic. |
| Brotman Baty Institute, |
RCV001076151 | SCV001241846 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |