Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575783 | SCV000674897 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-26 | criteria provided, single submitter | clinical testing | The p.L160F variant (also known as c.478C>T), located in coding exon 3 of the RET gene, results from a C to T substitution at nucleotide position 478. The leucine at codon 160 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, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001243228 | SCV001416370 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 160 of the RET protein (p.Leu160Phe). This variant is present in population databases (rs747536732, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 486343). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Center for Genomic Medicine, |
RCV002268204 | SCV002550379 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003233748 | SCV003931100 | uncertain significance | not provided | 2022-12-06 | 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; This variant is associated with the following publications: (PMID: 14633923) |
| All of Us Research Program, |
RCV001243228 | SCV004842939 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-11-30 | criteria provided, single submitter | clinical testing |