Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000546772 | SCV000635906 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1199 of the BRCA1 protein (p.Ala1199Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 462614). 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. 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. |
University of Washington Department of Laboratory Medicine, |
RCV003157703 | SCV003848292 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
Ambry Genetics | RCV003302812 | SCV003994160 | uncertain significance | Inborn genetic diseases | 2023-06-05 | criteria provided, single submitter | clinical testing | The c.3595G>T (p.A1199S) alteration is located in exon 10 (coding exon 9) of the BRCA1 gene. This alteration results from a G to T substitution at nucleotide position 3595, causing the alanine (A) at amino acid position 1199 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |