ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.643_646del (p.Thr215fs) (rs794728640)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182437 SCV000234782 pathogenic not provided 2018-03-08 criteria provided, single submitter clinical testing This deletion of four nucleotides in MEN1 is denoted c.628_631delACAG at the cDNA level and p.Thr210SerfsX13 (T210SfsX13) at the protein level. Using alternate nomenclature, this variant has been published as MEN1 738del4, MEN1 735del4 and MEN1 c.625_629delCAGA. The normal sequence, with the bases that are deleted in brackets, is CCAG[delACAG]TCAA. The deletion causes a frameshift which changes a Threonine to a Serine at codon 210, and creates a premature stop codon at position 13 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MEN1 c.628_631delACAG has been published in multiple unrelated families from several different ethnicities as a pathogenic variant in individuals with a clinical diagnosis of MEN1, often histologically confirmed with multiple associated tumor types (Chandrasekharappa 1997, Giraud 1998, Sakurai 1998, Mutch 1999, Cavaco 2002, Kouvaraki 2002, Wautot 2002, Cebrian 2003, Ellard 2005, Cardinal 2005). This variant has also been described as a recurrent MEN1 variant, occurring in at least 2.5% of affected MEN1 families (Lemos 2008, Thakker 2010). We consider this variant to be pathogenic.
Invitae RCV000018163 SCV000541231 pathogenic Multiple endocrine neoplasia, type 1 2019-10-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr210Serfs*13) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This particular variant has been reported in the literature in individuals affected with multiple endocrine neoplasia type 1 (PMID: 10664520, 9709921, 23154721, 17879353, 22026581, 25309785). This variant is also known in the literature as 738del4. ClinVar contains an entry for this variant (Variation ID: 200997). Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 17853334,12112656). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000491752 SCV000579631 pathogenic Hereditary cancer-predisposing syndrome 2019-01-31 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Genetic Services Laboratory,University of Chicago RCV000018163 SCV000595774 pathogenic Multiple endocrine neoplasia, type 1 2016-11-30 criteria provided, single submitter clinical testing
OMIM RCV000018163 SCV000038442 pathogenic Multiple endocrine neoplasia, type 1 1997-04-18 no assertion criteria provided literature only

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