ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1633C>T (p.Pro545Ser) (rs745404679)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575915 SCV000664573 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence,Other data supporting pathogenic classification,Other data supporting benign classification
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735331 SCV000854485 uncertain significance Leukodystrophy; Dystonia; Developmental regression; Abnormality of the cerebral white matter criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000679251 SCV000338793 uncertain significance not provided 2016-01-08 criteria provided, single submitter clinical testing
Invitae RCV000231689 SCV000291288 uncertain significance Multiple endocrine neoplasia, type 1 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 540 of the MEN1 protein (p.Pro540Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs745404679, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with multiple endocrine neoplasia type 1 (MEN1) (PMID: 12652570), an individual affected with sporadic pituitary macroadenoma (PMID: 23321498), and individuals in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 200987). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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.
Mendelics RCV000231689 SCV000838449 uncertain significance Multiple endocrine neoplasia, type 1 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000679251 SCV000805922 uncertain significance not provided 2017-10-27 criteria provided, single submitter clinical testing

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