Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166825 | SCV000217639 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-11-06 | criteria provided, single submitter | clinical testing | The p.I446L variant (also known as c.1336A>C), located in coding exon 8 of the BRIP1 gene, results from an A to C substitution at nucleotide position 1336. The isoleucine at codon 446 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well 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. |
Mendelics | RCV000709550 | SCV000839383 | uncertain significance | Fanconi anemia complementation group J | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001047345 | SCV001211296 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-11-21 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, 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 BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 187131). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with leucine at codon 446 of the BRIP1 protein (p.Ile446Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. |