ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1915G>A (p.Ala639Thr) (rs777122776)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226795 SCV000290539 uncertain significance Multiple endocrine neoplasia, type 2 2018-07-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 639 of the RET protein (p.Ala639Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs777122776, ExAC 0.005%). This variant has been reported in an individual affected with medullary thyroid carcinoma, and classified as likely benign based on segregation analysis (data not shown) (PMID: 26321248). ClinVar contains an entry for this variant (Variation ID: 241341). 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 threonine 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.
Counsyl RCV000409197 SCV000489941 uncertain significance Multiple endocrine neoplasia, type 2b 2016-08-16 criteria provided, single submitter clinical testing
Counsyl RCV000410332 SCV000489942 uncertain significance Multiple endocrine neoplasia, type 2a 2016-08-16 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679725 SCV000807015 uncertain significance not provided 2017-12-13 criteria provided, single submitter clinical testing

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