Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570153 | SCV000661095 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-11-02 | criteria provided, single submitter | clinical testing | The p.S1211C variant (also known as c.3632C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3632. The serine at codon 1211 is replaced by cysteine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is 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 | RCV000706771 | SCV000835841 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-19 | 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: 479240). 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 serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1211 of the BRCA1 protein (p.Ser1211Cys). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307545 | SCV002600446 | uncertain significance | not specified | 2022-10-11 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.3632C>G (p.Ser1211Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251278 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3632C>G has been reported in the literature as a presumed somatic occurrence in an individual affected with ovarian endometrioid carcinoma (Gaia-Oltean_2021). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| University of Washington Department of Laboratory Medicine, |
RCV000570153 | SCV003846508 | 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). |