ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.415C>T (p.His139Tyr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001224950 SCV001397180 likely pathogenic Multiple endocrine neoplasia, type 1 2019-05-17 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 139 of the MEN1 protein (p.His139Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with MEN1-related disease (PMID: 9215689, 30324798). Experimental studies have shown that this missense change alters MEN1 protein function (PMID: 12112656, 12509449). This variant disrupts the p.His139 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 21917868, 12746426, 10617276), 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.

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