Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031135 | SCV000300033 | 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. |
Labcorp Genetics |
RCV000048361 | SCV000076374 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-11-08 | 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: 37554). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 12491487, 25428789). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys1290*) 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). |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000031135 | SCV000325775 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000048361 | SCV000699078 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-08-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.3868A>T (p.Lys1290X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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 (c.3893C>A, p.Ser1298X; c.3937C>T, p.Gln1313X; c.4015G>T, p.Glu1339X). The variant was absent in 251164 control chromosomes (gnomAD). The variant, c.3868A>T, has been reported in the literature in individuals affected with breast cancer and/or ovarian cancer (Judkins_2005, Olopade_2003, Churpek_2015, Mgbemena_2017, Rebbeck_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions including one expert panel (ENIGMA) (evaluation after 2014) classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Ambry Genetics | RCV002354175 | SCV002620016 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | The p.K1290* pathogenic mutation (also known as c.3868A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3868. This changes the amino acid from a lysine to a stop codon within coding exon 9. This mutation has been identified in an African American woman diagnosed with early-onset breast cancer (Churpek JE et al, Breast Cancer Res. Treat. 2015 Jan; 149(1):31-9). 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. |
Baylor Genetics | RCV000031135 | SCV004215132 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-05-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV004700290 | SCV005201804 | pathogenic | not provided | 2023-08-30 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 3987A>T; This variant is associated with the following publications: (PMID: 29446198, 28122244, 25428789, 12491487, 20104584, 16267036) |
Sharing Clinical Reports Project |
RCV000031135 | SCV000053734 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-03-17 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031135 | SCV000144905 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | ||
Research Molecular Genetics Laboratory, |
RCV000048361 | SCV000587353 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
CZECANCA consortium | RCV001271016 | SCV001451829 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing |