ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1323G>T (p.Trp441Cys) (rs398124435)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790656 SCV000331189 pathogenic not provided 2015-08-31 criteria provided, single submitter clinical testing
Invitae RCV000318762 SCV000541191 likely pathogenic Multiple endocrine neoplasia, type 1 2019-01-08 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 436 of the MEN1 protein (p.Trp436Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with multiple endocrine neoplasia type 1 (PMID: 15714081, Invitae). This variant has been reported to affect MEN1 protein function (PMID: 22090276). This variant disrupts the p.Trp436 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been observed in individuals with MEN1-related conditions (PMID: 9103196, 21819486, 21127195), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000491855 SCV000579634 pathogenic Hereditary cancer-predisposing syndrome 2017-06-23 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,Well-characterized mutation at same position,Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Structural Evidence

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