Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002417633 | SCV002729918 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-30 | criteria provided, single submitter | clinical testing | The p.D707E variant (also known as c.2121T>A), located in coding exon 11 of the RET gene, results from a T to A substitution at nucleotide position 2121. The aspartic acid at codon 707 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration was reported in multiple individuals diagnosed with medullary thyroid cancer with or without pheochromocytoma from a large Han Chinese family; however, this variant was not present in all affected individuals (Zhang L et al. Pathobiology. 2017 Nov;84:152-160). This alteration was also detected in numerous individuals with medullary thyroid cancer in a large, extended Chinese family; however, all individuals with this variant also had RET p.C634Y, a well-established pathogenic alteration associated with multiple endocrine neoplasia type 2 phenotype (Lu F et al. Oncol Lett. 2017 Sep;14:3552-3558; Kloos et al. Thyroid. 2009 Jun;19:565-612). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |