Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002435695 | SCV002750792 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-28 | criteria provided, single submitter | clinical testing | The c.1010_1017delAGACCTCG pathogenic mutation, located in coding exon 5 of the RET gene, results from a deletion of 8 nucleotides at nucleotide positions 1010 to 1017, causing a translational frameshift with a predicted alternate stop codon (p.E337Gfs*14). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Loss-of-function variants in RET are known to cause Hirschsprung disease; however, such associations with Multiple Endocrine Neoplasia Type-2 (MEN2) have not been observed (Amiel J and Lyonnet S. J Med Genet. 2001 Nov;38(11):729-39; Wagner SM et al. Clinics (Sao Paulo). 2012;67 Suppl 1(Suppl 1):77-84). Based on the supporting evidence, this alteration is pathogenic for Hirschsprung disease; however, the association of this alteration with MEN2 is unlikely. |