Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000112771 | SCV000299474 | 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 |
RCV000049094 | SCV000077107 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser229Leufs*5) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 24578176, 27553291). This variant is also known as 804delT. ClinVar contains an entry for this variant (Variation ID: 55666). For these reasons, this variant has been classified as Pathogenic. |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112771 | SCV000326391 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000112771 | SCV000487837 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-11-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000486620 | SCV000568432 | pathogenic | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in BRCA1 is denoted c.685delT at the cDNA level and p.Ser229LeufsX5 (S229LfsX5) at the protein level. Using alternate nomenclature this variant would be defined as BRCA1 804delT. The normal sequence, with the base that is deleted in brackets, is ATTT[delT]CTGA. The deletion causes a frameshift which changes a Serine to a Leucine at codon 229, and creates a premature stop codon at position 5 of the new reading frame. It is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.685delT has been observed two individuals with triple negative breast cancer (Rashid 2016). We consider this variant to be pathogenic. |
| Color Diagnostics, |
RCV001178319 | SCV001342720 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000049094 | SCV001360725 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-09-23 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.685delT (p.Ser229LeufsX5) 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. The variant was absent in 246068 control chromosomes (gnomAD). c.685delT has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Rashid_2016, Singh_2018, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) including one expert panel (ENIGMA) cite the variant as pathogenic (4x)/likely pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001798250 | SCV002043463 | pathogenic | Breast and/or ovarian cancer | 2020-08-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001178319 | SCV002666051 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-05 | criteria provided, single submitter | clinical testing | The c.685delT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 685, causing a translational frameshift with a predicted alternate stop codon (p.S229Lfs*5). This alteration was identified in multiple individuals diagnosed with breast and/or ovarian cancer (Rashid MU et al. BMC Cancer, 2016 08;16:673; Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 | RCV000112771 | SCV004216995 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-02-15 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000112771 | SCV000145664 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-12-22 | no assertion criteria provided | clinical testing | |
| Cancer Genomics Lab, |
RCV000049094 | SCV004011753 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-03-30 | no assertion criteria provided | clinical testing |