ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1150C>G (p.Pro384Ala) (rs536298339)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567892 SCV000674890 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000412082 SCV000489895 uncertain significance Multiple endocrine neoplasia, type 2b 2016-07-14 criteria provided, single submitter clinical testing
Counsyl RCV000410243 SCV000489896 uncertain significance Multiple endocrine neoplasia, type 2a 2016-07-14 criteria provided, single submitter clinical testing
Invitae RCV000197885 SCV000255042 uncertain significance Multiple endocrine neoplasia, type 2 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 384 of the RET protein (p.Pro384Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs536298339, ExAC 0.03%) but has not been reported in the literature in individuals with a RET-related disease. ClinVar contains an entry for this variant (Variation ID: 216713). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The alanine 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. 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.

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