Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570795 | SCV000664515 | likely benign | Hereditary cancer-predisposing syndrome | 2019-01-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Mendelics | RCV000709106 | SCV000838375 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001046577 | SCV001210484 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 338 of the RET protein (p.Thr338Ile). This variant is present in population databases (rs377767433, gnomAD 0.005%). This missense change has been observed in individual(s) with Hirschsprung's disease and micromedullary thyroid carcinoma (PMID: 11955539, 21810974). ClinVar contains an entry for this variant (Variation ID: 38594). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change does not substantially affect RET function (PMID: 21810974, 25440022). 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. |
Institute of Human Genetics, |
RCV001262456 | SCV001440343 | likely benign | Multiple endocrine neoplasia, type 2b | 2019-01-01 | criteria provided, single submitter | clinical testing |