ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1467C>A (p.Asp489Glu) (rs372648203)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123298 SCV000166605 uncertain significance Multiple endocrine neoplasia, type 2 2019-11-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 489 of the RET protein (p.Asp489Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs372648203, ExAC 0.002%). This variant has not been reported in the literature in individuals with RET-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Mendelics RCV000709113 SCV000838383 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011534 SCV001171867 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-12 criteria provided, single submitter clinical testing Insufficient evidence

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