Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000257077 | SCV000323398 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-10-18 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000257077 | SCV000325245 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985381 | SCV001133514 | pathogenic | not provided | 2019-07-16 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient in literature, and not found in general population data. |
Ambry Genetics | RCV002418098 | SCV002729946 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-20 | criteria provided, single submitter | clinical testing | The c.2125_2126insAGT pathogenic mutation (also known as p.S708_F709ins*), located in coding exon 9 of the BRCA1 gene, results from an in-frame AGT insertion at nucleotide positions 2125 to 2126. This results in the insertion of stop codon between codons 708 and 709. This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). This alteration was also reported in an individual with breast cancer who had a relative with ovarian cancer (Crawford B et al. Breast Cancer Res. Treat., 2017 Jun;163:383-390). 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. |
Invitae | RCV002518776 | SCV003340165 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-05-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe709*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 266220). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28281021). |