ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.266_286del (p.Leu89_Ala95del) (rs1064792906)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460992 SCV000541186 uncertain significance Multiple endocrine neoplasia, type 1 2016-12-19 criteria provided, single submitter clinical testing This sequence change deletes 21 nucleotides from exon 2 of the MEN1 mRNA (c.266_286del). This leads to the deletion of 7 amino acid residues from the MEN1 protein (p.Leu89_Ala95del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with multiple endocrine neoplasia type 1 in 3 members of a single family (PMID: 17555499). This variant is also known as 375del21 in the literature. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, this is a rare in-frame deletion with uncertain impact on protein function that has been reported in an affected family. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000478848 SCV000572477 likely pathogenic not provided 2016-12-14 criteria provided, single submitter clinical testing The c.266_286del21 variant in the MEN1 gene has previously been reported in association with multiple endocrine neoplasia type 1 (Lourenco et al., 2007; Toledo et al., 2007; Coutinho et al., 2010). This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.266_286del21 variant is an in-frame deletion that results in the loss of seven amino acids, denoted p.Leu89_Ala95del. Five of the deleted residues are conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on currently available evidence, c.266_286del21 is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded.

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