Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756338 | SCV000884115 | likely pathogenic | not provided | 2018-01-23 | criteria provided, single submitter | clinical testing | The MEN1 c.125G>T; p.Gly42Val variant is reported in the literature in 3 individuals from two unrelated families affected with Multiple Endocrine Neoplasia Type 1 (Itoh 2017, Koehler 2017). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, other variants at this codon (p.Gly42Asp, p.Gly42Ser, p.Gly42Ala, p.Gly42Cys) have been reported in individuals with a clinical diagnosis of Multiple Endocrine Neoplasia Type 1 and all would be classified at least likely pathogenic (Anselmo 2016, Bassett 1998, Kong 2016, Kytola 2001, Wautot 2002). The glycine at codon 42 is highly conserved and computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be deleterious. Based on available information, this variant is considered likely pathogenic. References: Anselmo J et al. A novel germline mutation of the MEN 1 gene associated with multiple endocrine neoplasia type 1 (MEN1 syndrome) followed over three generations of a family. Endocrine Abstracts. 2016; 40. Bassett J et al. Characterization of mutations in patients with multiple endocrine neoplasia type 1. Am J Hum Genet. 1998 Feb; 62(2): 232–244. Itoh M et al. A novel MEN1 mutation in a Japanese adolescent with multiple endocrine neoplasia type 1. Clin Pediatr Endocrinol. 2017 Jan;26(1):25-28. Koehler V et al. Novel Germline p.Gly42Val MEN1 Mutation in a Family with Multiple Endocrine Neoplasia Type 1 - Excellent Response of Prolactinoma to Cabergoline. Ann Clin Lab Sci. 2017 Sep;47(5):606-610. Kong J et al. Clinical and Genetic Analysis of Multiple Endocrine Neoplasia Type 1-Related Primary Hyperparathyroidism in Chinese. PLoS One. 2016; 11(11): e0166634. Kytola S et al. Founder effect in multiple endocrine neoplasia type 1 (MEN 1) in Finland. J Med Genet. 2001 Mar;38(3):185-9. Masatsune Itoh and Yutaka Saikawa. A novel MEN1 mutation in a Japanese adolescent with multiple endocrine neoplasia type 1. Clin Pediatr Endocrinol. 2017 Jan; 26(1): 25-28. Wautot V et al. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Hum Mutat. 2002 Jul;20(1):35-47. |