Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001986833 | SCV002280034 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 478 of the RET protein (p.Cys478Tyr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with medullary thyroid cancer (PMID: 27525386). ClinVar contains an entry for this variant (Variation ID: 1493908). 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. 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. |
| Ambry Genetics | RCV002389005 | SCV002702821 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-23 | criteria provided, single submitter | clinical testing | The p.C478Y variant (also known as c.1433G>A), located in coding exon 7 of the RET gene, results from a G to A substitution at nucleotide position 1433. The cysteine at codon 478 is replaced by tyrosine, an amino acid with highly dissimilar properties. This alteration has been identified in an individual diagnosed with medullary thyroid cancer (Sherman SI et al. Cancer, 2016 Dec;122:3856-3864). 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. |