ClinVar Miner

Submissions for variant NM_001166108.2(PALLD):c.2651T>C (p.Met884Thr)

gnomAD frequency: 0.00003  dbSNP: rs587780200
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000116050 SCV000149959 uncertain significance not provided 2014-01-06 criteria provided, single submitter clinical testing PALLD has been only recently described in association with pancreatic cancer and the risks are not well understood. This variant is denoted PALLD c.2600T>C at the cDNA level, p.Met867Thr (M867T) at the protein level, and results in the change of a Methionine to a Threonine (ATG>ACG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALLD Met867Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution in which a neutral non-polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is located in the Immunoglobulin I-set domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the PALLD gene, remain unclear.
Invitae RCV000531519 SCV000656931 uncertain significance Pancreatic adenocarcinoma 2021-06-08 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with PALLD-related disease. ClinVar contains an entry for this variant (Variation ID: 128106). This variant is present in population databases (rs587780200, ExAC 0.007%). This sequence change replaces methionine with threonine at codon 380 of the PALLD protein (p.Met380Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine.
Ambry Genetics RCV004019617 SCV003855247 uncertain significance not specified 2022-11-04 criteria provided, single submitter clinical testing The p.M867T variant (also known as c.2600T>C), located in coding exon 14 of the PALLD gene, results from a T to C substitution at nucleotide position 2600. The methionine at codon 867 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.