Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019953 | SCV001181373 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-02 | criteria provided, single submitter | clinical testing | The p.H333Y variant (also known as c.997C>T), located in coding exon 5 of the RET gene, results from a C to T substitution at nucleotide position 997. The histidine at codon 333 is replaced by tyrosine, 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. |
| Labcorp Genetics |
RCV003532350 | SCV004280823 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-08-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RET-related conditions. 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: 823588). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 333 of the RET protein (p.His333Tyr). |