ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1642G>A (p.Gly548Ser) (rs374461212)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123300 SCV000166607 uncertain significance Multiple endocrine neoplasia, type 2 2018-09-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 548 of the RET protein (p.Gly548Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs374461212, ExAC 0.03%). This variant has been observed in several individuals affected with clinical features of multiple endocrine neoplasia type 2 (PMID: 28946813). ClinVar contains an entry for this variant (Variation ID: 136102). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Counsyl RCV000662401 SCV000784819 uncertain significance Multiple endocrine neoplasia, type 2a 2017-01-05 criteria provided, single submitter clinical testing
Mendelics RCV000662401 SCV000838387 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001012544 SCV001173011 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-19 criteria provided, single submitter clinical testing Insufficient evidence
Research and Development, ARUP Laboratories RCV000123300 SCV000788269 pathogenic Multiple endocrine neoplasia, type 2 2019-05-01 no assertion criteria provided literature only Two unrelated French individual reports: 1 MTC only (53 yr), and 1 with MTC and Pheo (53 yr). Described as VUS.

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