Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565892 | SCV000661126 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-04-25 | criteria provided, single submitter | clinical testing | The p.W385* variant (also known as c.1154G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1154. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This alteration has been reported in 1 of 240 patients considered high-risk patients for hereditary breast and ovarian cancer (Schenkel LC et al. J Mol Diagn, 2016 Sep;18:657-67). An alteration at the same codon, also resulting in a stop codon at amino acid 385 (c.1155G>A) has been reported in an individual diagnosed with premenopausal breast cancer (Francies FZ et al. BMC Cancer, 2015 Nov;15:912) and an individual from a breast and/or ovarian cancer cohort (Mannan AU et al. J. Hum. Genet., 2016 Jun;61:515-22). 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 | RCV001036173 | SCV001199524 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-04-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). A different variant (c.1155G>A) giving rise to the same protein effect observed here (p.Trp385*) has been determined to be pathogenic (PMID:26577449). This suggests that this variant is also likely to be causative of disease. This variant has been observed in several individuals undergoing genetic testing for hereditary breast and ovarian cancer (PMID: 26911350, 29310832). ClinVar contains an entry for this variant (Variation ID: 479259). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp385*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. |