ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1016C>T (p.Ser339Leu) (rs774829203)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000663096 SCV000786201 uncertain significance Multiple endocrine neoplasia, type 2a 2018-03-16 criteria provided, single submitter clinical testing
Invitae RCV000818592 SCV000959214 uncertain significance Multiple endocrine neoplasia, type 2 2018-11-02 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 339 of the RET protein (p.Ser339Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs774829203, ExAC 0.01%). This variant has been observed in an individual affected with Hirschsprung disease (PMID: 22174939). ClinVar contains an entry for this variant (Variation ID: 548870). 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 leucine 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, 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.

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