ClinVar Miner

Submissions for variant NM_020975.6(RET):c.652C>T (p.Pro218Ser)

gnomAD frequency: 0.00001  dbSNP: rs1009392744
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709103 SCV000838370 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV001052830 SCV001217060 uncertain significance Multiple endocrine neoplasia, type 2 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 218 of the RET protein (p.Pro218Ser). This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 584745). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002360840 SCV002657932 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-09 criteria provided, single submitter clinical testing The p.P218S variant (also known as c.652C>T), located in coding exon 4 of the RET gene, results from a C to T substitution at nucleotide position 652. The proline at codon 218 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002477638 SCV002792365 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a 2022-02-03 criteria provided, single submitter clinical testing

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