ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.845C>A (p.Pro282His) (rs1060499973)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471154 SCV000541179 uncertain significance Multiple endocrine neoplasia, type 1 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 277 of the MEN1 protein (p.Pro277His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two out of three affected individuals from a family affected with primary hyperparathyroidism (PHPT) additional affected and unaffected family members were not tested. Therefore, segregation with disease was not established (PMID: 12016470). ClinVar contains an entry for this variant (Variation ID: 403801). Functional analysis suggests that this variant results in reduced protein levels compared to wild type MEN1 protein (PMID: 21819486). In summary, this variant has been reported in a family in some individuals with PHPT and it may result in reduced MEN1 protein levels. However, in the absence of additional functional and/or segregation data, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000568673 SCV000673668 likely pathogenic Hereditary cancer-predisposing syndrome 2018-03-06 criteria provided, single submitter clinical testing Deficient protein function in appropriate functional assay(s);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation

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