ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1A>G (p.Met1Val) (rs386134250)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030198 SCV000052865 likely pathogenic Multiple endocrine neoplasia, type 1 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
GeneDx RCV000480514 SCV000566017 likely pathogenic not provided 2017-03-08 criteria provided, single submitter clinical testing The c.1 A>G variant in the MEN1 gene has previously been reported in at least one individual undergoing genetic testing for multiple endocrine neoplasia type 1 (Klein et al., 2005). This variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" to signify that it is not known if the loss of Met1 prevents all protein translation or if an abnormal protein is produced using an alternate Methionine codon. Based on currently available evidence, we consider c.1A>G to be a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded."
Ambry Genetics RCV000491918 SCV000579617 pathogenic Hereditary cancer-predisposing syndrome 2017-03-30 criteria provided, single submitter clinical testing The p.M1? pathogenic mutation (also known as c.1A>G) is located in coding exon 1 of the MEN1 gene and results from a A to G substitution at nucleotide position 1. This alters the methionine residue at the initiation codon. This pathogenic mutation has been reported in a family with familial isolated hyperparathyroidism. Note: In this paper the M1? (c.1A>G) pathogenic mutation was incorrectly referred to as L112V; however HGMD and the authors of this paper have verified that this represents the same mutation (Villablanca A et al. Eur. J. Endocrinol. 2002 Sep; 147(3):313-22). This pathogenic mutation has also been reported in another affected family however specific clinical information was not provided (Klein RD et al. Genet. Med. 2005 Feb; 7(2):131-8). In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, this alteration is interpreted as a disease-causing mutation.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000508430 SCV000604210 pathogenic not specified 2016-12-13 criteria provided, single submitter clinical testing
Invitae RCV000030198 SCV000753247 pathogenic Multiple endocrine neoplasia, type 1 2020-08-22 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the MEN1 mRNA. The next in-frame methionine is located at codon 228. This variant is not present in population databases (ExAC no frequency). Disruption of the initiator methionine has been observed in several individuals affected with multiple endocrine neoplasia, type 1 (PMID: 28736585, 29036195, Invitae). ClinVar contains an entry for this variant (Variation ID: 36525). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect - Invitae Patient Insights Network RCV000030198 SCV001749849 not provided Multiple endocrine neoplasia, type 1 no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 06-15-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000480514 SCV001928119 pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000480514 SCV001953485 likely pathogenic not provided no assertion criteria provided clinical testing

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