ClinVar

Description

This deletion of one nucleotide in PALB2 is denoted c.3362delG at the cDNA level and p.Gly1121ValfsX3 (G1121VfsX3) at the protein level. The normal sequence, with the base that is deleted in braces, is GAAG{G}TGAC. The deletion causes a frameshift, which changes a Glycine to a Valine at codon 1121, and creates a premature stop codon at position 3 of the new reading frame. Even though this frameshift occurs in the last exon of the gene, it is significant since the last 66 correct amino acids are lost; furthermore, truncating pathogenic variants downstream of this one have been identified in other breast/pancreatic families (Rahman 2007, Peterlongo 2011). This variant is predicted to cause loss of normal protein function through protein truncation. This variant has been reported in families with a history of breast cancer, with at least one family also having a history of pancreatic cancer (Blanco 2013, Janatova 2013, Antoniou 2014, Castera 2014, Thompson 2015). We consider this variant to be pathogenic.