Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000509701 | SCV000607952 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing | The p.Q1299H variant (also known as c.3897G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3897. The glutamine at codon 1299 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV000509701 | SCV003849527 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
Invitae | RCV003764751 | SCV004664852 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1299 of the BRCA1 protein (p.Gln1299His). This variant is not present in population databases (gnomAD no frequency). 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: 91618). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Sharing Clinical Reports Project |
RCV000077135 | SCV000108932 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-08-27 | no assertion criteria provided | clinical testing | |
Genome |
RCV003483465 | SCV004228935 | not provided | not provided | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 10-05-2015 by Lab Myriad. 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. |