ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1052T>A (p.Val351Glu)

gnomAD frequency: 0.00001  dbSNP: rs749449032
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000205293 SCV000259862 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 351 of the RET protein (p.Val351Glu). This variant is present in population databases (rs749449032, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 219791). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002399761 SCV002706117 likely benign Hereditary cancer-predisposing syndrome 2023-06-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153481 SCV003843452 benign Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV003462370 SCV004206717 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-06-16 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004791326 SCV005403659 likely benign Multiple endocrine neoplasia type 2A 2024-08-07 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

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