Submissions for variant NM_001370259.2(MEN1):c.912+2T>A

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702984	SCV005202204	likely pathogenic	Multiple endocrine neoplasia, type 1	2024-07-01	criteria provided, single submitter	clinical testing	Variant summary: MEN1 c.912+2T>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250772 control chromosomes (gnomAD). c.912+2T>A has been reported in the literature in a tumor sample from a study of familial hyperparathyroidism associated mutations without confirmation of a germline origin (Howell_2006). This report does not provide unequivocal conclusions about association of the variant with Multiple Endocrine Neoplasia Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 17065424). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.