Submissions for variant NM_001370259.2(MEN1):c.784-19TC[2]

dbSNP: rs764290037

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182400	SCV000234743	benign	not specified	2013-06-12	criteria provided, single submitter	clinical testing	The variant is found in MEN1 panel(s).
Counsyl	RCV000409712	SCV000488118	uncertain significance	Multiple endocrine neoplasia, type 1	2015-12-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000409712	SCV002347254	likely benign	Multiple endocrine neoplasia, type 1	2025-01-28	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000182400	SCV002760492	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000409712	SCV005427777	likely benign	Multiple endocrine neoplasia, type 1	2024-09-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000182400	SCV005884988	likely benign	not specified	2024-12-20	criteria provided, single submitter	clinical testing	Variant summary: MEN1 c.784-15_784-14delTC alters a nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00022 in 248156 control chromosomes (gnomAD). The observed variant frequency is approximately 10-fold of the estimated maximal expected allele frequency for a pathogenic variant in MEN1 causing Multiple Endocrine Neoplasia Type 1/Familial Isolated Hyperparthyroidism phenotype (2.1e-05). c.784-15_784-14delTC has been reported in the literature in individuals affected with Multiple Endocrine Neoplasia Type 1/Familial Isolated Hyperparthyroidism without evidence of cosegregation with disease (e.g. Cetani_2006, Jager_2006). These reports do not provide unequivocal conclusions about association of the variant with Multiple Endocrine Neoplasia Type 1/Familial Isolated Hyperparthyroidism. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16430712, 16563611). ClinVar contains an entry for this variant (Variation ID: 200968). Based on the evidence outlined above, the variant was classified as likely benign.
Myriad Genetics, Inc.	RCV000409712	SCV005895474	likely benign	Multiple endocrine neoplasia, type 1	2024-11-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529754	SCV001743767	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001529754	SCV001809016	likely benign	not provided		no assertion criteria provided	clinical testing