Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000807201 | SCV000947243 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 688 of the RET protein (p.Ser688Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with bilateral multicystic renal dysplasia (PMID: 28566479). ClinVar contains an entry for this variant (Variation ID: 651776). 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 | RCV002422770 | SCV002725142 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-08 | criteria provided, single submitter | clinical testing | The p.S688F variant (also known as c.2063C>T), located in coding exon 11 of the RET gene, results from a C to T substitution at nucleotide position 2063. The serine at codon 688 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was reported in a patient with bilateral multicystic renal dysplasia and was inherited from an unaffected father (Heidet L et al. J Am Soc Nephrol, 2017 Oct;28:2901-2914). 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. |