Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575489 | SCV000674860 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-05-10 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence |
| Mendelics | RCV000709102 | SCV000838369 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000812605 | SCV000952923 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2018-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 151 of the RET protein (p.Asn151Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs150261092, ExAC 0.006%). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 486321). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |