Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215869 | SCV000277941 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-19 | criteria provided, single submitter | clinical testing | The p.I504M variant (also known as c.1512C>G), located in coding exon 10 of the BRIP1 gene, results from a C to G substitution at nucleotide position 1512. The isoleucine at codon 504 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001350822 | SCV001545241 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 504 of the BRIP1 protein (p.Ile504Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 233545). 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 methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Gene |
RCV003225046 | SCV003921754 | uncertain significance | not provided | 2023-04-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |