Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000198118 | SCV000255045 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-10-27 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 216716). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 563 of the RET protein (p.Lys563Thr). |
| Ambry Genetics | RCV002408884 | SCV002715888 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-27 | criteria provided, single submitter | clinical testing | The p.K563T variant (also known as c.1688A>C), located in coding exon 9 of the RET gene, results from an A to C substitution at nucleotide position 1688. The lysine at codon 563 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |