Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565511 | SCV000668241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-13 | criteria provided, single submitter | clinical testing | The p.H471Y variant (also known as c.1411C>T), located in coding exon 6 of the BARD1 gene, results from a C to T substitution at nucleotide position 1411. The histidine at codon 471 is replaced by tyrosine, an amino acid with similar properties. This variant was found in 1/3236 epthelial ovarian cancer cases and 0/3431 unaffected controls (Ramus SJ et al. J. Natl. Cancer Inst. 2015 Nov;107(11)). This amino acid position is not 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. |
| Labcorp Genetics |
RCV000687465 | SCV000815030 | uncertain significance | Familial cancer of breast | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 471 of the BARD1 protein (p.His471Tyr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 482805). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |