Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001227910 | SCV001400289 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-05-02 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 955299). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 635 of the BRIP1 protein (p.Leu635Met). |
Ambry Genetics | RCV004032620 | SCV005029185 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-24 | criteria provided, single submitter | clinical testing | The p.L635M variant (also known as c.1903C>A), located in coding exon 12 of the BRIP1 gene, results from a C to A substitution at nucleotide position 1903. The leucine at codon 635 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |