Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055158 | SCV001219530 | pathogenic | Multiple endocrine neoplasia, type 1 | 2021-10-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individuals with multiple endocrine neoplasia, type 1 (PMID: 28736585, 29036195; Invitae; UMD). This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the MEN1 mRNA. The next in-frame methionine is located at codon 228. |
| Ambry Genetics | RCV003380824 | SCV004096999 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.1A>C) is located in coding exon 1 of the MEN1 gene and results from a A to C substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). Different substitutions impacting the same initiation codon (c.1A>G, c.1A>T, c.2T>C and c.2T>G) have been detected in individuals with features or clinical diagnoses of multiple endocrine neoplasia type 1 and familial isolated hyperparathyroidism (Ambry internal data; Villablanca A et al. Eur. J. Endocrinol. 2002 Sep;147(3):313-22; Klein RD et al. Genet. Med. 2005 Feb;7(2):131-8; Ventura M et al. Arch Endocrinol Metab, 2019 Sep;63:516-523; Romanet P et al. J Clin Endocrinol Metab, 2019 03;104:753-764). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |