Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077145 | SCV000300107 | 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 |
RCV000159991 | SCV000210175 | pathogenic | not provided | 2017-11-28 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.4354A>T at the cDNA level and p.Lys1452Ter (K1452X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also defined as BRCA1 4473A>T using alternate nomenclature, has not, to our knowledge, been reported in the literature. We consider it to be pathogenic. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000077145 | SCV000325927 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000700553 | SCV000829312 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-04-08 | 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: 91628). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys1452*) 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 | RCV002326792 | SCV002627927 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-11-26 | criteria provided, single submitter | clinical testing | The p.K1452* pathogenic mutation (also known as c.4354A>T), located in coding exon 11 of the BRCA1 gene, results from an A to T substitution at nucleotide position 4354. This changes the amino acid from a lysine to a stop codon within coding exon 11. This variant has been identified in multiple families diagnosed with breast and/or ovarian cancer (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620; Copson ER et al. Lancet Oncol. 2018 02;19:169-180). 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. |
Sharing Clinical Reports Project |
RCV000077145 | SCV000108942 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2007-09-04 | no assertion criteria provided | clinical testing |