Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000221098 | SCV000276660 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-23 | criteria provided, single submitter | clinical testing | The p.H107P variant (also known as c.320A>C), located in coding exon 3 of the BRIP1 gene, results from an A to C substitution at nucleotide position 320. The histidine at codon 107 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. 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 p.H107P remains unclear. |
Labcorp Genetics |
RCV001040448 | SCV001204024 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-02-04 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 232507). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with proline at codon 107 of the BRIP1 protein (p.His107Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. |