ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.307del (p.Leu103fs) (rs794728639)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182435 SCV000234780 pathogenic not provided 2018-07-26 criteria provided, single submitter clinical testing This deletion of one nucleotide in MEN1 is denoted c.307delC at the cDNA level and p.Leu103CysfsX16 (L103CfsX16) at the protein level. The normal sequence, with the base that is deleted in brackets, is CGAC[delC]TGTC. The deletion causes a frameshift which changes a Leucine to a Cysteine at codon 103, and creates a premature stop codon at position 16 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.307delC, also published as MEN1 c.416del and MEN1 c.417delC, has been observed in association with multiple endocrine neoplasia syndrome type 1 (Agarwal 1997, Chandrasekharappa 1997. Teh 1998, Mutch 1999, Wautot 2002, Benito 2005, Schaaf 2007). We consider this variant to be pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000182435 SCV000341446 pathogenic not provided 2016-04-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491671 SCV000579622 pathogenic Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000018159 SCV000628077 pathogenic Multiple endocrine neoplasia, type 1 2019-12-23 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 2 of the MEN1 mRNA (c.307delC), causing a frameshift at codon 103. This creates a premature translational stop signal (p.Leu103Cysfs*16) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEN1 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with multiple endocrine neoplasia type 1 (PMID: 9103196, 15522929, 17853334). This variant is also known as 416delC and 417delC in the literature. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000018159 SCV000711426 pathogenic Multiple endocrine neoplasia, type 1 2017-07-24 criteria provided, single submitter clinical testing The p.Leu103fs variant in MEN1 has been reported in 3 individuals with multiple endocrine neoplasia type 1 (MEN1; Chandrasekharappa 1997, Benito 2005) and has a lso been reported by other clinical laboratories in ClinVar (Variation ID 200996 ). It was absent from large population studies, though the ability of these stud ies to accurately detect indels may be limited. This variant is predicted to cau se a frameshift, which alters the protein?s amino acid sequence beginning at pos ition 103 and leads to a premature termination codon 16 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Hete rozygous loss of function of the MEN1 gene is an established disease mechanism i n MEN1 syndrome. In summary, this variant meets criteria to be classified as pat hogenic for MEN1 in an autosomal dominant manner based upon the predicted impact to the protein and absence from controls.
OMIM RCV000018159 SCV000038438 pathogenic Multiple endocrine neoplasia, type 1 1997-04-18 no assertion criteria provided literature only

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