ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1187C>T (p.Ser396Leu) (rs781646869)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410233 SCV000489793 uncertain significance Multiple endocrine neoplasia, type 2b 2016-03-11 criteria provided, single submitter clinical testing
Counsyl RCV000411297 SCV000489794 uncertain significance Multiple endocrine neoplasia, type 2a 2016-03-11 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507135 SCV000605033 uncertain significance not specified 2017-03-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000574133 SCV000674874 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000689688 SCV000817351 uncertain significance Multiple endocrine neoplasia, type 2 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 396 of the RET protein (p.Ser396Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Hirschsprung disease (PMID: 22648184). ClinVar contains an entry for this variant (Variation ID: 372081). 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 disruptive, 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.

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