Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164838 | SCV000215521 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-23 | criteria provided, single submitter | clinical testing | The p.T464I variant (also known as c.1391C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 1391. The threonine at codon 464 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000164838 | SCV000682954 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-29 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 464 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on 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 been identified in 1/251096 chromosomes 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. |
| Invitae | RCV001308704 | SCV001498170 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-06-15 | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 54237). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). This variant is present in population databases (rs62625301, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 464 of the BRCA1 protein (p.Thr464Ile). |
| University of Washington Department of Laboratory Medicine, |
RCV000164838 | SCV003851328 | 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). |
| Breast Cancer Information Core |
RCV000111605 | SCV000144080 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-12-17 | no assertion criteria provided | clinical testing |