Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218323 | SCV000275660 | likely benign | Hereditary cancer-predisposing syndrome | 2022-03-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV000687386 | SCV000814950 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 29 of the BRCA1 protein (p.Glu29Gly). This variant is present in population databases (rs773841328, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 231722). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30219179). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
ARUP Laboratories, |
RCV001812635 | SCV001477631 | uncertain significance | not provided | 2020-06-16 | criteria provided, single submitter | clinical testing | The BRCA1 c.86A>G; p.Glu29Gly variant (rs773841328), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 231722). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamic acid at codon 29 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, in vitro functional analyses demonstrate little effect on homology directed repair activity (Starita 2018). Due to limited information, the clinical significance of the p.Glu29Gly variant is uncertain at this time. References: Starita LM et al. A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function. Am J Hum Genet. 2018;103(4):498-508. |
Brotman Baty Institute, |
RCV001076955 | SCV001242807 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro | ||
Genome |
RCV001812635 | SCV004228481 | not provided | not provided | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 07-04-2016 by Lab Ambry Genetics. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |