Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688929 | SCV000816560 | uncertain significance | Familial cancer of breast | 2021-03-12 | 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, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PALB2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 268 of the PALB2 protein (p.Lys268Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. |
Color Diagnostics, |
RCV000772300 | SCV000905418 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 268 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PALB2-related disorders in the literature. This variant has not been identified 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. |
Ambry Genetics | RCV000772300 | SCV002681149 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-01 | criteria provided, single submitter | clinical testing | The p.K268E variant (also known as c.802A>G), located in coding exon 4 of the PALB2 gene, results from an A to G substitution at nucleotide position 802. The lysine at codon 268 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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. |