Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479667 | SCV000566449 | uncertain significance | not provided | 2021-07-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with breast cancer (Mehta 2018); This variant is associated with the following publications: (PMID: 27535533, 30555256) |
| Color Diagnostics, |
RCV000774939 | SCV000909009 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with tyrosine at codon 1618 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. A homology-mediated repair based assay reported intermediate activity for this variant protein (PMID: 35196514). This variant has been reported in an individual affected with ovarian cancer (PMID: 30555256). This variant has been identified in 1/251386 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV001223802 | SCV001395968 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-27 | 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 1618 of the BRCA1 protein (p.His1618Tyr). This variant is present in population databases (rs755920262, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 30555256). This variant is also known as c.4915C>T (p.His1639Tyr). ClinVar contains an entry for this variant (Variation ID: 418981). 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. 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. |
| Ambry Genetics | RCV000774939 | SCV002634116 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing | The p.H1618Y variant (also known as c.4852C>T), located in coding exon 14 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4852. The histidine at codon 1618 is replaced by tyrosine, an amino acid with similar properties. 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. |
| Baylor Genetics | RCV003476156 | SCV004212669 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-10-30 | criteria provided, single submitter | clinical testing |