Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000214112 | SCV000277611 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-07 | criteria provided, single submitter | clinical testing | The p.R238G variant (also known as c.712A>G), located in coding exon 4 of the PALB2 gene, results from an A to G substitution at nucleotide position 712. The arginine at codon 238 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved on limited sequence alignment. 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 |
RCV000692131 | SCV000819940 | uncertain significance | Familial cancer of breast | 2024-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 238 of the PALB2 protein (p.Arg238Gly). This variant is present in population databases (rs779278389, gnomAD 0.01%). 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: 233268). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Gene |
RCV001566064 | SCV001789531 | uncertain significance | not provided | 2019-06-13 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
| Fulgent Genetics, |
RCV002485431 | SCV002778198 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 | 2022-03-01 | criteria provided, single submitter | clinical testing |