Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159966 | SCV000210125 | uncertain significance | not provided | 2014-08-26 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.2259T>G at the cDNA level, p.Ser753Arg (S753R) at the protein level, and results in the change of a Serine to an Arginine (AGT>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Ser753Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Ser753Arg occurs at a position that is poorly conserved across species. It is not located in a known functional domain although this position is a modified phosphoserine residue (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA1 Ser753Arg is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV002444663 | SCV002736528 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-26 | criteria provided, single submitter | clinical testing | The p.S753R variant (also known as c.2259T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 2259. The serine at codon 753 is replaced by arginine, an amino acid with dissimilar properties. 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. |
University of Washington Department of Laboratory Medicine, |
RCV002444663 | SCV003847807 | 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). |