Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000473049 | SCV000549263 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-02-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1566 of the BRCA1 protein (p.Ser1566Tyr). 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: 409298). 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. 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. |
Counsyl | RCV000662893 | SCV000785810 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-12-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001022911 | SCV001184706 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-10-26 | criteria provided, single submitter | clinical testing | The p.S1566Y variant (also known as c.4697C>A), located in coding exon 14 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4697. The serine at codon 1566 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is highly 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. |
Preventiongenetics, |
RCV003418188 | SCV004118628 | uncertain significance | BRCA1-related condition | 2022-08-26 | criteria provided, single submitter | clinical testing | The BRCA1 c.4697C>A variant is predicted to result in the amino acid substitution p.Ser1566Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Color Diagnostics, |
RCV001022911 | SCV004360158 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with tyrosine at codon 1566 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). 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. |
MGZ Medical Genetics Center | RCV003607286 | SCV004543876 | likely benign | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP |