ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1943T>C (p.Val648Ala)

dbSNP: rs864622505
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000204329 SCV000260876 uncertain significance Multiple endocrine neoplasia, type 2 2015-09-27 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 648 of the RET protein (p.Val648Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the germline of affected individuals. 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: "Benign"; Align-GVGD: "Class C25"). In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV004760436 SCV005370105 uncertain significance not provided 2023-06-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14633923)

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