Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001064073 | SCV001228949 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 858239). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 24569164, 26884819). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. This missense change has been observed in individual(s) with breast cancer (PMID: 26884819). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 194 of the BRCA1 protein (p.Ala194Val). |
| Revvity Omics, |
RCV003145325 | SCV003830128 | uncertain significance | not provided | 2022-09-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003372972 | SCV004093329 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | The p.A194V variant (also known as c.581C>T), located in coding exon 7 of the BRCA1 gene, results from a C to T substitution at nucleotide position 581. The alanine at codon 194 is replaced by valine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with breast cancer (Wong-Brown M et al. Hered Cancer Clin Pract, 2016 Feb;14:6). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |