Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000774646 | SCV000908512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamine at codon 149 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 been identified in 2/282742 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 | RCV001358808 | SCV001554660 | uncertain significance | Familial cancer of breast | 2022-10-12 | 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 629857). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is present in population databases (rs770680919, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 149 of the PALB2 protein (p.Lys149Gln). |
Ambry Genetics | RCV000774646 | SCV005029057 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-11 | criteria provided, single submitter | clinical testing | The p.K149Q variant (also known as c.445A>C), located in coding exon 4 of the PALB2 gene, results from an A to C substitution at nucleotide position 445. The lysine at codon 149 is replaced by glutamine, 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. |