Annotation Detail
Information
- Associated Genes
- RET
- Associated Variants
-
RET p.Cys609Tyr (p.C609Y)
(
ENST00000355710.8,
ENST00000340058.6,
ENST00000713926.1,
ENST00000615310.5 )
RET p.Cys609Tyr (p.C609Y) ( ENST00000340058.6, ENST00000355710.8, ENST00000615310.5, ENST00000713926.1 ) - Associated Disease
- thyroid gland medullary carcinoma
- Source Database
- CIViC Evidence
- Description
- Study of a family with three generations of history indicating co-segregation of RET C609Y and multiple endocrine neoplasia type 2A, many of whom exhibited medullary thyroid cancers specifically. 22 individuals in this family were carriers of C609Y. Of these, 9 exhibited medullary thyroid cancers. While the variant is strongly suspected of being pathogenic for these tumors, this variant appears to result in later onset of cancer than some other variants and the authors recommend delaying prophylactic thyroidectomy until 10-15 years of age. In addition to this large family, the authors also provide an extensive review of prior reports of C609 variants, identifying a total of 111 patients from 19 publications, representing 21 affected kindreds and 15 sporadic cases. 89 of these cases had C609Y specifically. The authors also summarize prior functional work that suggests that C609Y has transforming activity that is significant but not as strong as some other variants. Based on all of this analysis, the authors conclude that C609Y causes medullary thyroid cancers but a milder form than some other variants. Based on this paper, the following ACMG evidence codes seem potentially valid: 'PS1', 'PS3', 'PM5', 'PP1', 'PP4', and 'PP5'.
- Variant Origin
- germline
- Variant Origin
- Rare Germline
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/2913
- Gene URL
- https://civic.genome.wustl.edu/links/genes/42
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1260
- Rating
- 4
- Evidence Type
- Predisposing
- Disease
- Thyroid Gland Medullary Carcinoma
- Evidence Direction
- Supports
- Evidence Level
- B
- Clinical Significance
- Pathogenic
- Pubmed
- 19472011
Drugs