Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000074580 | SCV000108665 | uncertain significance | not provided | 2017-11-27 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.339C>G at the cDNA level, p.Asn113Lys (N113K) at the protein level, and results in the change of an Asparagine to a Lysine (AAC>AAG). Using alternate nomenclature, this variant would be defined as BRCA1 458C>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Asn113Lys was not observed in large population cohorts (Lek 2016). Since Asparagine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Asn113Lys is located in the BRD7 binding domain (Harte 2010). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Asn113Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Ambry Genetics | RCV000564284 | SCV000665839 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | The p.N113K variant (also known as c.339C>G), located in coding exon 5 of the BRCA1 gene, results from a C to G substitution at nucleotide position 339. The asparagine at codon 113 is replaced by lysine, an amino acid with similar properties. This amino acid position is not 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 this alteration remains unclear. |
| Invitae | RCV001043000 | SCV001206710 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-03-16 | 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. 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 BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 89058). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 113 of the BRCA1 protein (p.Asn113Lys). |
| Baylor Genetics | RCV003474656 | SCV004212762 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-09-15 | criteria provided, single submitter | clinical testing |