ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1267G>A (p.Gly423Arg) (rs767601598)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662983 SCV000785968 uncertain significance Multiple endocrine neoplasia, type 2a 2018-02-16 criteria provided, single submitter clinical testing
Invitae RCV000704241 SCV000833182 uncertain significance Multiple endocrine neoplasia, type 2 2018-06-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 423 of the RET protein (p.Gly423Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs767601598, ExAC 0.006%). This variant has been observed in individuals affected with Hirschsprung disease (PMID: 21995290, 22174939). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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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