ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3048T>G (p.Phe1016Leu)

dbSNP: rs1567212918
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679768 SCV000807102 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV001018293 SCV001179510 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-29 criteria provided, single submitter clinical testing The p.F1016L variant (also known as c.3048T>G), located in coding exon 10 of the PALB2 gene, results from a T to G substitution at nucleotide position 3048. The phenylalanine at codon 1016 is replaced by leucine, 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 (formerly Invitae), Labcorp RCV001861873 SCV002158547 uncertain significance Familial cancer of breast 2024-07-08 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1016 of the PALB2 protein (p.Phe1016Leu). This variant is not present in population databases (gnomAD no frequency). 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: 560875). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PALB2 protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV005019168 SCV005646466 uncertain significance Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3; Breast-ovarian cancer, familial, susceptibility to, 5 2024-03-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.