ClinVar

Description

The c.2388delT pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of one nucleotide at position 2388, causing a translational frameshift with a predicted alternate stop codon (p.V797Lfs*15). This alteration has been reported in the literature in 1 of 101 unrelated patients affected by colorectal cancer or an HNPCC-associated cancer (endometrium, small bowel, urinary tract); authors suggest that this mutation may be specific for Polish families as it had not been previously described at the time of publication (Kurzawski G et al, J. Med. Genet. 2002 Oct; 39(10):E65). A detailed clinical case study on a woman with this exact mutation and multiple primary tumors (7) suggest these patients do not succumb to other extracolonic cancers, provided they are regularly followed-up (Janavicius R et al, Hered Cancer Clin Pract 2012 ; 10(1):1). This alteration has also been reported in a female diagnosed with MMR deficient colorectal cancer at age 30 and having a family history of HNPCC-associated cancers (Pearlman R et al. JAMA Oncol, 2017 Apr;3:464-471). 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.