Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003361060 | SCV004056428 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-15 | criteria provided, single submitter | clinical testing | The p.Q681* pathogenic mutation (also known as c.2041C>T), located in coding exon 11 of the RET gene, results from a C to T substitution at nucleotide position 2041. This changes the amino acid from a glutamine to a stop codon within coding exon 11. 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 S 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. |