Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000510083 | SCV000607788 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-04-14 | criteria provided, single submitter | clinical testing | The p.N268K variant (also known as c.804C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 804. The asparagine at codon 268 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is not 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. |
Color Diagnostics, |
RCV000510083 | SCV000688664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-23 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985447 | SCV001133647 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000099 (3/30418 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 26306726 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
Invitae | RCV001857299 | SCV002143163 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs771076131, gnomAD 0.01%). This missense change has been observed in individual(s) with breast and ovarian cancer (PMID: 26306726, 29020660). ClinVar contains an entry for this variant (Variation ID: 441285). 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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 32546644). 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. This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 268 of the BRCA1 protein (p.Asn268Lys). |
University of Washington Department of Laboratory Medicine, |
RCV000510083 | SCV003847929 | 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). |
KCCC/NGS Laboratory, |
RCV003227773 | SCV003924372 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-05-15 | criteria provided, single submitter | clinical testing | a variant of uncertain significance was detected in the BRCA1 gene (c.804C>G). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 268 of the BRCA1 protein (p.Asn268Lys). This variant is present in population databases (rs771076131, gnomAD 0.01%). This missense change has been observed in individual(s) with breast and ovarian cancer (PMID: 26306726, 29020660). ClinVar contains an entry for this variant (Variation ID: 441285). This amino acid position is not well conserved ( PhyloP=2.65) . In addition, this alteration is predicted to be tolerated by in silico analysis. 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. |
MGZ Medical Genetics Center | RCV003607297 | SCV004543885 | benign | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: BP1_STR, BS3 |