Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002037784 | SCV002228476 | pathogenic | Multiple endocrine neoplasia, type 1 | 2020-11-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces tryptophan with cysteine at codon 183 of the MEN1 protein (p.Trp183Cys). 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 individual(s) with multiple endocrine neoplasia type 1 (PMID: 16699310, 22281890, 11524904). 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 variant disrupts the p.Trp183 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been observed in individuals with MEN1-related conditions (PMID: 10576763, 28663159, 9215690), which suggests that this may be a clinically significant amino acid residue. |