Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000661054 | SCV000783301 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-12-15 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Invitae | RCV000233519 | SCV000289765 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-04-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.His971Argfs*20) 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: 240783). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000481177 | SCV000570594 | pathogenic | not provided | 2016-06-06 | criteria provided, single submitter | clinical testing | This deletion of 2 nucleotides in BRCA1 is denoted c.2912_2913delAT at the cDNA level and p.His971ArgfsX20 (H971RfsX20) at the protein level. The normal sequence, with the bases that are deleted in braces, is AAAC[AT]GGAC. The deletion causes a frameshift which changes a Histidine to an Arginine at codon 971, and creates a premature stop codon at position 20 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
| Ambry Genetics | RCV003165641 | SCV003856606 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | The c.2912_2913delAT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2912 to 2913, causing a translational frameshift with a predicted alternate stop codon (p.H971Rfs*20). 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. |
| Baylor Genetics | RCV000661054 | SCV004216845 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-01-30 | criteria provided, single submitter | clinical testing |