ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1267G>A (p.Asp423Asn) (rs104894264)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490854 SCV000579629 pathogenic 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,Deficient protein function in appropriate functional assay(s),Other strong data supporting pathogenic classification,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Integrated Genetics/Laboratory Corporation of America RCV000018183 SCV000052862 pathogenic Multiple endocrine neoplasia, type 1 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Invitae RCV000018183 SCV000291276 pathogenic Multiple endocrine neoplasia, type 1 2018-09-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 418 of the MEN1 protein (p.Asp418Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with multiple endocrine neoplasia type 1 (MEN1) in several families (PMID: 11303512, 11836268, 17766710), and has been described as a recurrent mutation in individuals affected with MEN1 (PMID: 12050235, 12652570, 12112656, 10762295, 9463336). ClinVar contains an entry for this variant (Variation ID: 16703). Experimental studies have shown that this missense change results in an unstable protein that is rapidly degraded by the ubiquitin-proteasome pathway (PMID: 15254225, 21819486). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000018183 SCV000712008 pathogenic Multiple endocrine neoplasia, type 1 2016-09-13 criteria provided, single submitter clinical testing The p.Asp423Asn variant in MEN1 has been reported in least 4 individuals with ME N1 and segregated with disease in at least 8 relatives from 1 family (Turner 200 2, Vierimaa 2007, Crepin 2003). It was also absent from large population studies . In vitro functional studies provide some evidence that the p.Asp423Asn variant may impact protein function (Shimazu 2011, Yaguchi 2004). In summary, this vari ant meets criteria to be classified as pathogenic for MEN1 in an autosomal domin ant manner based upon segregation studies, absence from controls, and functional evidence studies.
OMIM RCV000018183 SCV000038462 pathogenic Multiple endocrine neoplasia, type 1 2002-06-01 no assertion criteria provided literature only

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