Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002514098 | SCV003441424 | likely pathogenic | Multiple endocrine neoplasia, type 2 | 2022-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 32 of the RET protein (p.Ser32Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 7581377, 8114939). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13923). 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 affects RET function (PMID: 8654369, 8894691, 9681515, 20473317). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000014948 | SCV000035204 | risk factor | Hirschsprung disease, susceptibility to, 1 | 1994-01-27 | no assertion criteria provided | literature only | |
Clinical Molecular Genetics Laboratory, |
RCV000678742 | SCV000804914 | likely pathogenic | Aganglionic megacolon | 2014-07-29 | no assertion criteria provided | clinical testing |