ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1186dup (p.Cys396fs)

dbSNP: rs1555461413
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
Ambry Genetics RCV000454134 SCV000538138 pathogenic Hereditary cancer-predisposing syndrome 2018-02-21 criteria provided, single submitter clinical testing The c.1186dupT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a duplication of T at nucleotide position 1186, causing a translational frameshift with a predicted alternate stop codon (p.C396Lfs*5). This alteration was identified in a French patient with a personal and family history of breast cancer (Damiola F et al. Breast Cancer Res. Treat., 2015 Dec;154:463-71). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000685167 SCV000812640 pathogenic Familial cancer of breast 2023-10-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys396Leufs*5) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26564480). ClinVar contains an entry for this variant (Variation ID: 402291). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985883 SCV001134530 pathogenic not provided 2018-10-19 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data.
Myriad Genetics, Inc. RCV000685167 SCV004188551 pathogenic Familial cancer of breast 2023-09-08 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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.