Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001218751 | SCV001390649 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2019-07-20 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RET-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with glycine at codon 324 of the RET protein (p.Trp324Gly). The tryptophan residue is moderately conserved and there is a large physicochemical difference between tryptophan and glycine. |
| Ambry Genetics | RCV002375195 | SCV002692666 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-23 | criteria provided, single submitter | clinical testing | The p.W324G variant (also known as c.970T>G), located in coding exon 5 of the RET gene, results from a T to G substitution at nucleotide position 970. The tryptophan at codon 324 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is 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. |