Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000988348 | SCV001138034 | benign | Multiple endocrine neoplasia, type 2a | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002433465 | SCV002752096 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-18 | criteria provided, single submitter | clinical testing | The p.S922Y variant (also known as c.2765C>A), located in coding exon 16 of the RET gene, results from a C to A substitution at nucleotide position 2765. The serine at codon 922 is replaced by tyrosine, an amino acid with dissimilar properties. This alteration has been reported in a Japanese family with five females diagnosed with Hirschsprung’s disease (Kawano T et al. Pediatr Surg Int, 2017 Oct;33:1041-1046). This alteration has also been reported in a MEN2B patient, however another RET alteration, p.M918T (c.2753T>C) was also detected in this individual, and three other family members with only p.S922Y were asymptomatic (Kitamura Y et al. Hum Mol Genet, 1995 Oct;4:1987-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003764617 | SCV004613046 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 922 of the RET protein (p.Ser922Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Hirschsprung disease, type 1 (PMID: 28799054). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 24969). 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. |