Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002406105 | SCV002710770 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-11-04 | criteria provided, single submitter | clinical testing | The p.K563E variant (also known as c.1687A>G), located in coding exon 5 of the PALB2 gene, results from an A to G substitution at nucleotide position 1687. The lysine at codon 563 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been identified in a cohort of 3236 ovarian cancer patients, but was also observed in 1 of 3431 controls (Ramus SJ, J. et al. Natl. Cancer Inst. 2015 Nov; 107(11)). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6497 samples (12994 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 130000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is highly 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 p.K563E remains unclear. |
| Labcorp Genetics |
RCV003097115 | SCV003350144 | uncertain significance | Familial cancer of breast | 2022-04-28 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 563 of the PALB2 protein (p.Lys563Glu). |
| Fulgent Genetics, |
RCV005019196 | SCV005646491 | uncertain significance | Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3; Breast-ovarian cancer, familial, susceptibility to, 5 | 2024-06-05 | criteria provided, single submitter | clinical testing |