Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000256873 | SCV000323435 | 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 |
RCV000256873 | SCV000325320 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000812603 | SCV000952921 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-07-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser770*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several families with high risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 266246). A different variant (c.2309C>A) giving rise to the same protein effect observed here (p.Ser770*) has been reported in individuals affected with breast and ovarian cancer (PMID: 9808526, 10866029, 22006311, 25452441). It is also known as c.2428C>A in the literature. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002446502 | SCV002735574 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-29 | criteria provided, single submitter | clinical testing | The p.S770* pathogenic mutation (also known as c.2309C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2309. This changes the amino acid from a serine to a stop codon within coding exon 9. 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 variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |