Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002619735 | SCV003502945 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-02-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 134 of the BRCA2 protein (p.Leu134His). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. |
| Ambry Genetics | RCV004949012 | SCV005550129 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-15 | criteria provided, single submitter | clinical testing | The p.L134H variant (also known as c.401T>A), located in coding exon 3 of the BRCA2 gene, results from a T to A substitution at nucleotide position 401. The leucine at codon 134 is replaced by histidine, an amino acid with 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 variant remains unclear. |