ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3142C>G (p.Leu1048Val) (rs774347808)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410987 SCV000489785 uncertain significance Multiple endocrine neoplasia, type 2b 2016-02-12 criteria provided, single submitter clinical testing
Counsyl RCV000412050 SCV000489786 uncertain significance Multiple endocrine neoplasia, type 2a 2016-02-12 criteria provided, single submitter clinical testing
Invitae RCV000474558 SCV000543844 uncertain significance Multiple endocrine neoplasia, type 2 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 1048 of the RET protein (p.Leu1048Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs774347808, ExAC 0.002%). This variant has been reported in an individual affected with Hirschsprung disease (PMID: 22648184). ClinVar contains an entry for this variant (Variation ID: 372080). 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 RCV000574881 SCV000674751 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-03 criteria provided, single submitter clinical testing Insufficient evidence

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