ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.654+1G>T (rs794728622)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182411 SCV000234754 pathogenic not provided 2016-09-07 criteria provided, single submitter clinical testing The c.654+1 G>T splice site variant in the MEN1 gene has been previously reported in association with multiple endocrine neoplasia type 1 (MEN1) (for examples, see Teh et al., 1998a; Teh et al., 1998b; Cardinal et al., 2005). This variant destroys the canonical splice donor site in intron 3, and is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Based on currently available evidence, we consider c.654+1G>T to be pathogenic.
Mendelics RCV000709159 SCV000838458 pathogenic Multiple endocrine neoplasia, type 1 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV000709159 SCV000963141 pathogenic Multiple endocrine neoplasia, type 1 2018-07-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the MEN1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals and families affected with multiple endocrine neoplasia type 1 (PMID: 9709921, 15635078, 9064485, 9671073). This variant is also known as IVS3+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 200978). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). For these reasons, this variant has been classified as Pathogenic.

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