ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1162G>A (p.Val388Ile) (rs776223166)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000313283 SCV000362287 uncertain significance Pheochromocytoma 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000370252 SCV000362288 uncertain significance Multiple endocrine neoplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000393718 SCV000362289 uncertain significance Renal adysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000312196 SCV000362290 uncertain significance Hirschsprung Disease, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000654549 SCV000776443 uncertain significance Multiple endocrine neoplasia, type 2 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 388 of the RET protein (p.Val388Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs776223166, ExAC 0.009%). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 299891). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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