Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002513055 | SCV003441420 | pathogenic | Multiple endocrine neoplasia, type 2 | 2021-12-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys611 amino acid residue in RET. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8626834, 11331212, 20979234). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 13913). This missense change has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 2 (PMID: 8103403, 20979234, 27809725, 30763276). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 611 of the RET protein (p.Cys611Trp). |
OMIM | RCV000014932 | SCV000035188 | pathogenic | Multiple endocrine neoplasia type 2A | 1994-01-01 | no assertion criteria provided | literature only |