Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480364 | SCV000567534 | uncertain significance | not provided | 2023-11-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 7575T>G; This variant is associated with the following publications: (PMID: 32377563, 29884841) |
| Ambry Genetics | RCV001026304 | SCV001188657 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-30 | criteria provided, single submitter | clinical testing | The p.I2449M variant (also known as c.7347T>G), located in coding exon 13 of the BRCA2 gene, results from a T to G substitution at nucleotide position 7347. The isoleucine at codon 2449 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is poorly 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. |
| Labcorp Genetics |
RCV001851168 | SCV002264177 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2449 of the BRCA2 protein (p.Ile2449Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 419618). 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) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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. |
| Prevention |
RCV004527586 | SCV004111986 | uncertain significance | BRCA2-related disorder | 2023-02-28 | criteria provided, single submitter | clinical testing | The BRCA2 c.7347T>G variant is predicted to result in the amino acid substitution p.Ile2449Met. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is listed in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/419618/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| All of Us Research Program, |
RCV004002308 | SCV004833277 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-08-15 | criteria provided, single submitter | clinical testing |