Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001997182 | SCV002234907 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2021-04-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is present in population databases (rs759342879, ExAC 0.002%). This sequence change replaces threonine with serine at codon 562 of the RET protein (p.Thr562Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. |
Ambry Genetics | RCV004043880 | SCV005028356 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-08 | criteria provided, single submitter | clinical testing | The p.T562S variant (also known as c.1684A>T), located in coding exon 9 of the RET gene, results from an A to T substitution at nucleotide position 1684. The threonine at codon 562 is replaced by serine, 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. Based on the available evidence, the clinical significance of this alteration remains unclear. |