ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2543T>A (p.Met848Lys) (rs201101792)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034772 SCV000043477 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Counsyl RCV000663125 SCV000786259 uncertain significance Multiple endocrine neoplasia, type 2a 2018-03-30 criteria provided, single submitter clinical testing
Invitae RCV000698313 SCV000826973 uncertain significance Multiple endocrine neoplasia, type 2 2018-06-16 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 848 of the RET protein (p.Met848Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 41841). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional 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.

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