ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.1388A>C (p.Glu463Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
MGZ Medical Genetics Center RCV002290207 SCV002579377 uncertain significance Multiple endocrine neoplasia, type 1 2021-09-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002391402 SCV002702683 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-08 criteria provided, single submitter clinical testing The p.E463A variant (also known as c.1388A>C), located in coding exon 9 of the MEN1 gene, results from an A to C substitution at nucleotide position 1388. The glutamic acid at codon 463 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002290207 SCV005732891 uncertain significance Multiple endocrine neoplasia, type 1 2024-04-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 463 of the MEN1 protein (p.Glu463Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1709865). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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