Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000112086 | SCV000299938 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Gene |
RCV000236540 | SCV000294030 | pathogenic | not provided | 2016-03-01 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.3398T>A at the cDNA level and p.Leu1133Ter (L1133X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TAA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, a different nucleotide change at the same position, BRCA1 c.3398T>G, resulting in the same Leu1133Ter nonsense change has been reported in association with breast and/or ovarian cancer (Kroiss 2005). Based on the currently available information, BRCA1 Leu1133Ter is considered pathogenic. |
| Ambry Genetics | RCV001020190 | SCV001181637 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | The p.L1133* pathogenic mutation (also known as c.3398T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 3398. This changes the amino acid from a leucine to a stop codon within coding exon 9. While this exact alteration has not been reported in the literature, a different mutation resulting in the same stop codon (c.3398T>G) has been reported in individuals with Hereditary Breast and Ovarian Cancer Syndrome (HBOC) (Kroiss R et al. Hum. Mutat., 2005 Dec;26:583-9; Pölsler L et al. Eur. J. Hum. Genet., 2016 Feb;24:258-62; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). 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. |
| Color Diagnostics, |
RCV001020190 | SCV004360233 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-30 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A different nucleotide change, c.3398T>G, resulting in a premature termination codon at the same protein position, has been detected in several suspected hereditary breast and ovarian cancer families (PMID: 16287141, 26014432, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Breast Cancer Information Core |
RCV000112086 | SCV000144750 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing |