Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001209608 | SCV001381051 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 337 of the BRCA1 protein (p.Glu337Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. |
University of Washington Department of Laboratory Medicine, |
RCV003158482 | SCV003846233 | 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). |
Color Diagnostics, |
RCV003158482 | SCV004361085 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-06 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 337 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV003158482 | SCV005100567 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-12 | criteria provided, single submitter | clinical testing | The p.E337Q variant (also known as c.1009G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 1009. The glutamic acid at codon 337 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |