Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003531901 | SCV004294349 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-11-29 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects RET function (PMID: 8894691). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 13924). This missense change has been observed in individual(s) with Hirschprung disease (PMID: 7581377, 8114939). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 64 of the RET protein (p.Pro64Leu). 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. |
| OMIM | RCV000014949 | SCV000035205 | risk factor | Hirschsprung disease, susceptibility to, 1 | 1994-01-27 | no assertion criteria provided | literature only |