Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485312 | SCV000572605 | uncertain significance | not provided | 2017-01-03 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.5120T>G at the cDNA level, p.Ile1707Ser (I1707S) at the protein level, and results in the change of an Isoleucine to a Serine (ATT>AGT). Using alternate nomenclature, this variant would be defined as BRCA1 5239T>G. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA1 Ile1707Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Isoleucine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Ile1707Ser occurs at a position that is conserved in mammals and is located in the BRCT1 domain as well as a region known to interact with multiple proteins (Paul 2014, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Ile1707Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Invitae | RCV001058772 | SCV001223364 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-04-03 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with serine at codon 1707 of the BRCA1 protein (p.Ile1707Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 422989). This variant is not present in population databases (ExAC no frequency). |
| Baylor Genetics | RCV001072290 | SCV004212685 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-10-24 | criteria provided, single submitter | clinical testing | |
| Brotman Baty Institute, |
RCV001072290 | SCV001237644 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |