Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564070 | SCV000668610 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-10 | criteria provided, single submitter | clinical testing | The p.I3339V variant (also known as c.10015A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 10015. The isoleucine at codon 3339 is replaced by valine, 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 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is not conserved and valine is a reference amino acid in several 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 |
RCV001365279 | SCV001561544 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-06-20 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 483001). This variant is present in population databases (rs768567428, ExAC 0.006%). This sequence change replaces isoleucine with valine at codon 3339 of the BRCA2 protein (p.Ile3339Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. |