Submissions for variant NM_001370259.2(MEN1):c.1429dup (p.Glu477fs)

dbSNP: rs886041214

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000363690	SCV000329423	pathogenic	not provided	2017-12-27	criteria provided, single submitter	clinical testing	TThe c.1429dupG variant in the MEN1 gene has been previously reported in association with multiple endocrine neoplasia type 1 (Poncin et al., 1999). This duplication causes a frameshift starting with codon Glutamic Acid 477, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 54 of the new reading frame, denoted p.Glu477GlyfsX54. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1429dupG is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider c.1429dupG to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090323	SCV005835855	pathogenic	Multiple endocrine neoplasia, type 1	2024-02-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu477Glyfs*54) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 134 amino acid(s) of the MEN1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 9888389). This variant is also known as 1539insG. ClinVar contains an entry for this variant (Variation ID: 279851). This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Thr580Argfs*8) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.