ClinVar Miner

Submissions for variant NM_020975.6(RET):c.431G>A (p.Arg144His) (rs551142665)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000200522 SCV000255058 uncertain significance Multiple endocrine neoplasia, type 2 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 144 of the RET protein (p.Arg144His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs551142665, ExAC 0.03%). This variant has been reported in an individual affected with Hirschsprung disease (PMID: 26395553). ClinVar contains an entry for this variant (Variation ID: 216729). 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. 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 RCV000565710 SCV000674838 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Counsyl RCV000662542 SCV000785121 uncertain significance Multiple endocrine neoplasia, type 2a 2017-05-03 criteria provided, single submitter clinical testing

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