Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165469 | SCV000216200 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-03 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Gene |
RCV000485697 | SCV000571022 | uncertain significance | not provided | 2016-07-18 | criteria provided, single submitter | clinical testing | This variant is denoted BRIP1 c.1717C>G at the cDNA level, p.Leu573Val (L573V) at the protein level, and results in the change of a Leucine to a Valine (CTA>GTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Leu573Val 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 Leucine and Valine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Leu573Val occurs at a position that is not conserved and is within the Helicase domain (Cantor 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRIP1 Leu573Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV000533781 | SCV000633568 | uncertain significance | Familial cancer of breast; Fanconi anemia, complementation group J | 2019-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 573 of the BRIP1 protein (p.Leu573Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 185954). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |