Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000257600 | SCV000323528 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-10-18 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000257600 | SCV000325480 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000657439 | SCV000779174 | pathogenic | not provided | 2017-12-26 | criteria provided, single submitter | clinical testing | This duplication of one nucleotide in BRCA1 is denoted c.2861dupT at the cDNA level and p.Ser955IlefsX16 (S955IfsX16) at the protein level. The normal sequence, with the base that is duplicated in brackets, is TGTC[dupT]ATCA. The duplication causes a frameshift which changes a Serine to an Isoleucine at codon 955, and creates a premature stop codon at position 16 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779904 | SCV000916806 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2018-09-25 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.2861dupT (p.Ser955IlefsX16) 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 (eg. c.2864C>A, p.Ser955X; c.2868delT, p.Gln957fsX43; c.2901_2902dupTC, p.Pro968fsX33). The variant was absent in 246124 control chromosomes (gnomAD). The variant, c.2861dupT, has been reported in the literature in one family affected with Hereditary Breast and Ovarian Cancer (Azzollini_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Ambry Genetics | RCV001016813 | SCV001177811 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-05-10 | criteria provided, single submitter | clinical testing | The c.2861dupT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of T at nucleotide position 2861, causing a translational frameshift with a predicted alternate stop codon (p.S955Ifs*16). This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). 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. |
Invitae | RCV000779904 | SCV001401115 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-03-04 | 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: 266311). This premature translational stop signal has been observed in individual(s) with personal and/or family history of breast and/or ovarian cancer (PMID: 27062684). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser955Ilefs*16) 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). |
Baylor Genetics | RCV000257600 | SCV004211727 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2021-11-03 | criteria provided, single submitter | clinical testing |