Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000701617 | SCV000830427 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 317 of the RET protein (p.Thr317Met). This variant is present in population databases (rs760322514, gnomAD 0.003%). 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: 578566). 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 | RCV003380690 | SCV004090989 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-11 | criteria provided, single submitter | clinical testing | The p.T317M variant (also known as c.950C>T), located in coding exon 5 of the RET gene, results from a C to T substitution at nucleotide position 950. The threonine at codon 317 is replaced by methionine, an amino acid with similar properties. This amino acid position is highly 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. |
| Prevention |
RCV004527751 | SCV004108768 | uncertain significance | RET-related disorder | 2022-12-22 | criteria provided, single submitter | clinical testing | The RET c.950C>T variant is predicted to result in the amino acid substitution p.Thr317Met. To our knowledge, this variant has not bee reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-43601906-C-T) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/578566/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003460970 | SCV004208687 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-09-09 | criteria provided, single submitter | clinical testing |