Submissions for variant NM_001370259.2(MEN1):c.416A>C (p.His139Pro)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003062407	SCV003440329	likely pathogenic	Multiple endocrine neoplasia, type 1	2022-08-09	criteria provided, single submitter	clinical testing	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. This variant disrupts the p.His139 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9215689, 9989505, 12509449, 21917868). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function. This missense change has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 12746426). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 139 of the MEN1 protein (p.His139Pro).