Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041113 | SCV001204709 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-02-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1553Cysfs*6) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 839374). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002327275 | SCV002633714 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-15 | criteria provided, single submitter | clinical testing | The c.4658delT pathogenic mutation, located in coding exon 13 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 4658, causing a translational frameshift with a predicted alternate stop codon (p.L1553Cfs*6). This mutation has been reported in an individual diagnosed with epithelial ovarian cancer (Ashour M et al. Cancer Manag Res, 2019 Jul;11:6275-6284). 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. |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003339439 | SCV004048312 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | criteria provided, single submitter | clinical testing | The frame shift c.4721del(p.Leu1574CysfsTer6) variant in BRCA1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Leu1574CysfsTer6 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant causes a frameshift starting with codon Leucine 1574, changes this amino acid to Cysteine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Leu1574CysfsTer6. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. |