Submissions for variant NM_001370259.2(MEN1):c.399C>A (p.Tyr133Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004522720	SCV005030440	pathogenic	Hereditary cancer-predisposing syndrome	2024-01-26	criteria provided, single submitter	clinical testing	The p.Y133* pathogenic mutation (also known as c.399C>A), located in coding exon 1 of the MEN1 gene, results from a C to A substitution at nucleotide position 399. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. This variant has been observed in multiple individuals who met clinical criteria for multiple endocrine neoplasia type 1 (MEN1) (Wautot V et al. Hum Mutat, 2002 Jul;20:35-47; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV005249682	SCV005897046	pathogenic	Multiple endocrine neoplasia, type 1	2024-12-09	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.