Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001292634 | SCV001481226 | uncertain significance | Familial medullary thyroid carcinoma | 2020-01-13 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Labcorp Genetics |
RCV001863171 | SCV002117575 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2021-07-31 | 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 997472). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 648 of the RET protein (p.Val648Phe). The valine residue is weakly conserved and there is a small physicochemical difference between valine and phenylalanine. |
| Gene |
RCV003223715 | SCV003919245 | uncertain significance | not provided | 2022-10-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004035594 | SCV005028326 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-25 | criteria provided, single submitter | clinical testing | The p.V648F variant (also known as c.1942G>T), located in coding exon 11 of the RET gene, results from a G to T substitution at nucleotide position 1942. The valine at codon 648 is replaced by phenylalanine, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |