ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1322G>A (p.Trp441Ter) (rs104894260)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518947 SCV000617597 pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing This variant is denoted MEN1 c.1307G>A at the cDNA level and p.Trp436Ter (W436X) at the proteinlevel. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon(TGG>TAG), and is predicted to cause loss of normal protein function through protein truncation. This variant has beenreported several individuals with a personal and family history of multiple endocrine neoplasia type 1(Chandrasekharappa 1997, Mayr 1998, Schaaf 2007) and is considered pathogenic
Invitae RCV000018167 SCV001211956 pathogenic Multiple endocrine neoplasia, type 1 2019-12-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEN1 gene (p.Trp436*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 175 amino acids of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 9103196). ClinVar contains an entry for this variant (Variation ID: 16687). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the MEN1 protein. Other variant(s) that disrupt this region (p.Thr580Argfs*8) have been determined to be pathogenic (PMID: 15331604, 16449969, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018167 SCV000038446 pathogenic Multiple endocrine neoplasia, type 1 1997-04-18 no assertion criteria provided literature only

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