Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000654573 | SCV000776467 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-07-24 | criteria provided, single submitter | clinical testing | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 543738). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is present in population databases (rs760765930, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 966 of the RET protein (p.Thr966Ile). |
| Ambry Genetics | RCV002440389 | SCV002749681 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-16 | criteria provided, single submitter | clinical testing | The p.T966I variant (also known as c.2897C>T), located in coding exon 17 of the RET gene, results from a C to T substitution at nucleotide position 2897. The threonine at codon 966 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly 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. |