Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077060 | SCV000299571 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590574 | SCV000698843 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2017-07-24 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.1292delT (p.Leu431Tyrfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Glu1470X, p.Glu1535X, p.Tyr1703X, etc.). This variant has been reported in multiple individuals undergoing clinical testing of BRCA1/2 by clinical laboratories and during validation of assay methods (van der Stoep_2009, Mattocks_2010). This variant is absent in 121238 control chromosomes from ExAC. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic. |
Invitae | RCV000590574 | SCV000831016 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-06-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 91543). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu431Tyrfs*10) 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). |
Ambry Genetics | RCV002381391 | SCV002692836 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-03 | criteria provided, single submitter | clinical testing | The c.1292delT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1292, causing a translational frameshift with a predicted alternate stop codon (p.L431Yfs*10). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Sharing Clinical Reports Project |
RCV000077060 | SCV000108857 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2008-01-24 | no assertion criteria provided | clinical testing |