Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000567755 | SCV000661032 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-14 | criteria provided, single submitter | clinical testing | The c.1763_1764delGCinsAA variant (also known as p.S588K), located in coding exon 9 of the BRCA1 gene, results from an in-frame deletion of GC and insertion of AA at nucleotide positions 1763 to 1764. This results in the substitution of the serine residue for a lysine residue at codon 588, an amino acid with dissimilar properties. This alteration has been previously detected in a cohort of 381 unselected endometrial cancer patients who underwent multi-gene panel testing (Ring KL et al. Mod Pathol, 2016 11;29:1381-1389). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000567755 | SCV000682982 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001038109 | SCV001201557 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-09-20 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 479211). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces serine, which is neutral and polar, with lysine, which is basic and polar, at codon 588 of the BRCA1 protein (p.Ser588Lys). |
University of Washington Department of Laboratory Medicine, |
RCV000567755 | SCV003848034 | 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). |