Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563155 | SCV000661057 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-12 | criteria provided, single submitter | clinical testing | The p.M1652V variant (also known as c.4954A>G), located in coding exon 14 of the BRCA1 gene, results from an A to G substitution at nucleotide position 4954. The methionine at codon 1652 is replaced by valine, an amino acid with highly similar 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985425 | SCV001133600 | uncertain significance | not provided | 2019-03-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001858078 | SCV002193075 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1652 of the BRCA1 protein (p.Met1652Val). 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: 479222). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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. |
| Brotman Baty Institute, |
RCV001077349 | SCV001243263 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |