ClinVar

Description

The c.387_388delTC pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 387 to 388, causing a translational frameshift with a predicted alternate stop codon (p.Q130Vfs*2). One study identified three individuals heterozygous for this mutation in a Swiss HNPCC family: an individual diagnosed with colon cancer at age 57, an individual diagnosed with rectal cancer at age 46 who was also reported to have several adenomas of the colon, and an individual diagnosed with cancers of the nasopharynx and colon at ages 24 and 43, respectively. Furthermore, one untested obligate carrier in the family was reported to have a glioblastoma multiforme consistent with Turcot's syndrome (Buerstedde JM et al. J. Med. Genet. 1995 Nov;32(11):909-12). An additional study identified this mutation in a single individual with demonstrated absence of MSH2 protein on immunohistochemistry and low microsatellite instability on tumor testing (Lamberti C et al. Digestion 2006;74:58-67). This alteration was reported somatically in a sebaceous neoplasm with absent MSH2 and MSH6 protein (Joly MO et al. Hum. Mutat. 2015 Mar;36:292-5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.