ClinVar Miner

Submissions for variant NM_020975.6(RET):c.406G>A (p.Glu136Lys) (rs79014735)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571944 SCV000674779 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678743 SCV000804915 uncertain significance not specified 2011-03-18 no assertion criteria provided clinical testing
Counsyl RCV000662413 SCV000784845 uncertain significance Multiple endocrine neoplasia, type 2a 2017-01-04 criteria provided, single submitter clinical testing
Invitae RCV000197380 SCV000255056 uncertain significance Multiple endocrine neoplasia, type 2 2018-03-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 136 of the RET protein (p.Glu136Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs79014735, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 216727). 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.
PreventionGenetics RCV000679750 SCV000807054 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing

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