Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077578 | SCV000300141 | 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 |
RCV000235132 | SCV000210179 | pathogenic | not provided | 2019-09-25 | 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; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23096355, 29486991, 25525159, 11606101, 26183948, 28503720, 28049106, 22811390, 28127413, 29446198, 31209999, 31447099) |
Ambry Genetics | RCV000162879 | SCV000213366 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-24 | criteria provided, single submitter | clinical testing | The p.E1535* pathogenic mutation (also known as c.4603G>T), located in coding exon 13 of the BRCA1 gene, results from a G to T substitution at nucleotide position 4603. This changes the amino acid from a glutamic acid to a stop codon within coding exon 13. This mutation has been reported in several individuals with breast and/or ovarian cancer and one patient with breast and serous mixed endometrioid cancers (Schorge JO et al. Gynecol. Oncol. 2001 Nov;83:383-7; Pennington KP et al. Cancer. 2013 Jan;119:332-8; Rummel S et al. Breast Cancer Res. Treat. 2013 Jan;137:119-25; Dodova RI et al. BMC Cancer. 2015 Jul;15:523; Rummel SK et al. Breast Cancer Res. Treat. 2017 Aug;164:593-601; Rebbeck TR et al. Hum. Mutat. 2018 May;39:593-620; Barrington DA et al. Gynecol. Oncol. 2018 05;149:337-340). 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000077578 | SCV000326006 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000048603 | SCV000540929 | pathogenic | Familial cancer of breast | 2017-02-23 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000496846 | SCV000699159 | pathogenic | Hereditary breast ovarian cancer syndrome | 2016-04-04 | criteria provided, single submitter | clinical testing | Variant Summary: The variant in interest, c.4603G>T, is a nonsense mutation that leads to a premature termination at codon 1535. This variant has been reported in the literature and reputable databases at least 15 times and was not identified in large and broad ExAC control cohort. This variant is located in a close proximity to other known pathogenic variants, such as c.4609C>T (p.Gln1537X), c.4612C>T (p.Gln1538X), c.4618G>T (p.Glu1540X) and c.4621G>T (p.Glu1541X). These variants have been reported in UMD, BIC and HGMD at least 7 times with biological significance "5 - Causal", indicating that the variant in interest is located in a mutational hot spot. The variant in interest shows very strong evidence for pathogenicity: it is a truncating variant, located in a mutational hot spot and is absent from controls (ESP and 1000G). Taken together, this variant has been classified as a Pathogenic. |
Human Genome Sequencing Center Clinical Lab, |
RCV000077578 | SCV001434961 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-10-02 | criteria provided, single submitter | clinical testing | This c.4603G>T (p.Glu1535*) variant in the BRCA1 gene is predicted to introduce a premature translation termination codon. This variant is absent in the general population according to the gnomAD database. It has been reported in several unrelated patients with breast cancer or ovary cancer [PMID: 11606101, 22811390].Therefore, the c.4603G>T (p.Glu1535*) variant in the BRCA1 gene is classified as pathogenic. |
Invitae | RCV000496846 | SCV001585591 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-09-10 | criteria provided, single submitter | clinical testing | Studies have shown that this premature translational stop signal is associated with altered splicing resulting in unknown protein product impact (Invitae). ClinVar contains an entry for this variant (Variation ID: 55236). This premature translational stop signal has been observed in individual(s) with breast, ovarian, and uterine cancer (PMID: 11606101, 22811390, 26183948, 28503720). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1535*) 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). For these reasons, this variant has been classified as Pathogenic. |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000077578 | SCV004013215 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-04-05 | criteria provided, single submitter | clinical testing | PVS1, PS4, PM2 |
Baylor Genetics | RCV000077578 | SCV004215185 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-03-22 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000235132 | SCV004224827 | pathogenic | not provided | 2023-05-02 | criteria provided, single submitter | clinical testing | PP5, PM2, PVS1 |
Color Diagnostics, |
RCV000162879 | SCV004360166 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-21 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 14 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with early-onset and/or familial breast cancer (PMID: 11606101, 22811390, 23096355, 26183948, 28503720). 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. |
Sharing Clinical Reports Project |
RCV000077578 | SCV000109381 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-09-25 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077578 | SCV000145126 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496846 | SCV000587411 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research |