Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001220086 | SCV001392059 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 164 of the MEN1 protein (p.Ala164Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with multiple endocrine neoplasia type 1 (PMID: 9463336, 12112656, 20231234, 25309785). ClinVar contains an entry for this variant (Variation ID: 948764). 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. Experimental studies have shown that this missense change does not substantially affect MEN1 function (PMID: 12509449). For these reasons, this variant has been classified as Pathogenic. |