Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112218 | SCV000300047 | 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. |
Ambry Genetics | RCV000563165 | SCV000660947 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-10-21 | criteria provided, single submitter | clinical testing | The p.K1322* pathogenic mutation (also known as c.3964A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3964. This changes the amino acid from a lysine to a stop codon within coding exon 9. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590774 | SCV000699089 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2017-02-13 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.3964A>T (p.Lys1322X) 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. c.3972_3974delinsAA, c.4035delA, c.4041_4042delAG, c.4065_4068delTCAA, c.4096+3A>G). Mutation Taster predicts a damaging outcome for this variant. This variant is absent in 121396 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
Invitae | RCV000590774 | SCV001592839 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-05-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys1322*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55059). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
Breast Cancer Information Core |
RCV000112218 | SCV000144926 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing |