FMTC = familial medullary thyroid carcinoma; MEN2A = multiple endocrine neoplasia type 2A; MEN2B = multiple endocrine neoplasia type 2B; NA = not applicable

See Table A. Genes and Databases for chromosome locus and protein.

Since MEN2 occurs through a gain-of-function mechanism, gene-targeted deletion/duplication analysis is not indicated.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants, and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Sequence analysis of all RET exons may be performed instead of sequencing of select exons. If sequencing of select exons has been previously performed with no pathogenic variant detected, a multigene panel including RET is recommended (see Establishing the Diagnosis).

Zbuk & Eng [2007], Romei et al [2016], Elisei et al [2019]

Pathogenic variants of codons 618, 620, and 634 each account for 20%-30% of pathogenic variants. Other pathogenic variants in exons 5, 8, 10, 11, and 13-16 appear to account for a small percentage of pathogenic variants in families with FMTC, with an important minority affecting codons 768 and 804 [Wells et al 2015, Romei et al 2016, Elisei et al 2019].

Approximately 95% of individuals have a pathogenic variant at codon 918 in exon 16 [Eng et al 1996, Wells et al 2015]. A pathogenic variant in exon 15 has been identified in several affected individuals [Gimm et al 1997, Smith et al 1997, Wells et al 2015, Salvatore et al 2021].

Pathogenic variants in exons 10 and 11 [Eng et al 1996, Wells et al 2015, Romei et al 2016, Elisei et al 2019]

Pathogenic variants typically detected: p.Met918Thr, p.Ala883Phe. Note: Pathogenic variants included in a panel may vary by laboratory.