ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3448C>T (p.Leu1150Phe)

dbSNP: rs863224787
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198123 SCV000255105 uncertain significance Familial cancer of breast 2022-03-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1150 of the PALB2 protein (p.Leu1150Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 26283626). ClinVar contains an entry for this variant (Variation ID: 216755). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Cancer Genetics Laboratory, Peter MacCallum Cancer Centre RCV000198123 SCV000268029 uncertain significance Familial cancer of breast 2015-06-01 criteria provided, single submitter case-control
Color Diagnostics, LLC DBA Color Health RCV000776376 SCV000911814 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-18 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 1150 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 been detected in two breast cancer case-control studies in one affected individual and absent in unaffected control individuals, and in the largest of the two study it was found in 1/60466 cases and 0/53461 unaffected individuals (PMID: 26283626, 33471991; Leiden Open Variation Database DB-ID PALB2_010744). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284322 SCV001470044 uncertain significance not provided 2020-05-25 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000776376 SCV002531180 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-28 criteria provided, single submitter curation

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.