ClinVar Miner

Submissions for variant NM_020975.6(RET):c.973G>A (p.Ala325Thr) (rs779719517)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000528670 SCV000658505 uncertain significance Multiple endocrine neoplasia, type 2 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 325 of the RET protein (p.Ala325Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs779719517, ExAC 0.01%). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 477393). 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.
Ambry Genetics RCV000566312 SCV000674818 likely benign Hereditary cancer-predisposing syndrome 2017-05-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign)
Mendelics RCV000709105 SCV000838374 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing

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