Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000544076 | SCV000635451 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-05-26 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 462379). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 180 of the BRCA2 protein (p.Ile180Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. |
| Ambry Genetics | RCV000570587 | SCV000661316 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-06-23 | criteria provided, single submitter | clinical testing | The p.I180F variant (also known as c.538A>T), located in coding exon 6 of the BRCA2 gene, results from an A to T substitution at nucleotide position 538. The isoleucine at codon 180 is replaced by phenylalanine, an amino acid with highly 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 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000570587 | SCV000683701 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-02 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985545 | SCV001133828 | uncertain significance | not provided | 2019-04-24 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004568786 | SCV005059053 | uncertain significance | Familial cancer of breast | 2024-02-16 | criteria provided, single submitter | clinical testing |