Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000471187 | SCV000549867 | uncertain significance | Hereditary breast and ovarian cancer syndrome | 2018-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with asparagine at codon 203 of the BRCA2 protein (p.Thr203Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs398122547, ExAC 0.001%) but has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91437). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV000758918 | SCV000567749 | uncertain significance | not provided | 2018-08-24 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.608C>A at the cDNA level, p.Thr203Asn (T203N) at the protein level, and results in the change of a Threonine to an Asparagine (ACC>AAC). Using alternate nomenclature, this variant would be defined as BRCA2 836C>A. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Thr203Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Thr203Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Ambry Genetics | RCV000509879 | SCV000608010 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-01 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758918 | SCV000887864 | uncertain significance | not provided | 2017-12-26 | criteria provided, single submitter | clinical testing | |
| Color | RCV000509879 | SCV000905901 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-07 | criteria provided, single submitter | clinical testing | |
| Sharing Clinical Reports Project |
RCV000076954 | SCV000108751 | uncertain significance | Breast-ovarian cancer, familial 2 | 2012-09-04 | no assertion criteria provided | clinical testing |