Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213341 | SCV000274016 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-16 | criteria provided, single submitter | clinical testing | The p.Q838E variant (also known as c.2512C>G), located in coding exon 5 of the PALB2 gene, results from a C to G substitution at nucleotide position 2512. The glutamine at codon 838 is replaced by glutamic acid, an amino acid with highly similar properties. 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV000635607 | SCV000757026 | uncertain significance | Familial cancer of breast | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 838 of the PALB2 protein (p.Gln838Glu). This variant is present in population databases (rs750650768, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230460). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Color Diagnostics, |
RCV000213341 | SCV001340938 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-22 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with glutamic acid at codon 838 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). Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31406 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. |
| Fulgent Genetics, |
RCV002478788 | SCV002789057 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 | 2022-04-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003223625 | SCV003919659 | uncertain significance | not provided | 2023-04-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed in any cases, but was observed in unaffected controls from a breast cancer study (Decker et al., 2017); This variant is associated with the following publications: (PMID: 24485656, 19609323, 28779002) |
| Baylor Genetics | RCV000635607 | SCV004202186 | uncertain significance | Familial cancer of breast | 2023-06-30 | criteria provided, single submitter | clinical testing |