ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1462A>T (p.Thr488Ser) (rs753733901)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234316 SCV000290530 uncertain significance Multiple endocrine neoplasia, type 2 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 488 of the RET protein (p.Thr488Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs753733901, ExAC 0.009%) but has not been reported in the literature in individuals with a RET-related disease. This variant has been reported in exome sequencing of 1,643 cancer-free elderly individuals (PMID: 25425582). ClinVar contains an entry for this variant (Variation ID: 241336). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000709111 SCV000838381 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing

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