Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000823179 | SCV000964028 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-07-14 | 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 664982). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 19818148, 27062684, 29020660). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1701 of the BRCA1 protein (p.Leu1701Pro). |
| Ambry Genetics | RCV002336720 | SCV002644631 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-21 | criteria provided, single submitter | clinical testing | The p.L1701P variant (also known as c.5102T>C), located in coding exon 16 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5102. The leucine at codon 1701 is replaced by proline, an amino acid with similar properties. This alteration has been identified in cohorts of Italian patients diagnosed with breast and/or ovarian cancer (Santonocito C et al. Breast. 2017 Dec;36:74-78; Azzollini J et al. Eur. J. Intern. Med. 2016 Jul;32:65-71; Miolo G et al. BMC Cancer. 2009 Oct;9:360). Based on structural analysis, the L1701 residue is located in the important hydrophobic peptide binding pocket of the BRCA1 protein (Williams RS et al. Nat. Struct. Biol. 2004;11(6): 519-525). 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. |
| Brotman Baty Institute, |
RCV001076382 | SCV001242121 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |