Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564433 | SCV000674912 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-05-16 | criteria provided, single submitter | clinical testing | The p.L501F variant (also known as c.1501C>T), located in coding exon 7 of the RET gene, results from a C to T substitution at nucleotide position 1501. The leucine at codon 501 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly 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 |
RCV001853799 | SCV002135363 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2021-07-06 | 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 486354). 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 leucine with phenylalanine at codon 501 of the RET protein (p.Leu501Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. |