ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2887C>A (p.Leu963Ile) (rs864622603)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206385 SCV000261281 uncertain significance Multiple endocrine neoplasia, type 2 2018-04-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 963 of the RET protein (p.Leu963Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. 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: 220609). 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: "Probably 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 RCV000662412 SCV000784843 uncertain significance Multiple endocrine neoplasia, type 2a 2016-12-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV001016859 SCV001177858 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-26 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes)

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