ClinVar Miner

Submissions for variant NM_020975.6(RET):c.832A>G (p.Thr278Ala) (rs541929171)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662513 SCV000785052 uncertain significance Multiple endocrine neoplasia, type 2a 2017-03-28 criteria provided, single submitter clinical testing
Invitae RCV000205998 SCV000260576 uncertain significance Multiple endocrine neoplasia, type 2 2016-08-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 278 of the RET protein (p.Thr278Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs541929171, ExAC 0.02%). This variant has been reported in individuals affected with Hirschsprung disease (PMID: 22174939). ClinVar contains an entry for this variant (Variation ID: 220205). 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, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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