Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026724 | SCV001189161 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-26 | criteria provided, single submitter | clinical testing | The p.H257Y variant (also known as c.769C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 769. The histidine at codon 257 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly 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. |
| Invitae | RCV001202280 | SCV001373388 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-08-29 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 257 of the BRCA1 protein (p.His257Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| University of Washington Department of Laboratory Medicine, |
RCV001026724 | SCV003847956 | 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). |