ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.1673T>C (p.Met558Thr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003631631 SCV004405623 likely pathogenic Multiple endocrine neoplasia, type 1 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 558 of the MEN1 protein (p.Met558Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 1 (Invitae). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV004636796 SCV005131152 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-04 criteria provided, single submitter clinical testing The p.M558T variant (also known as c.1673T>C), located in coding exon 9 of the MEN1 gene, results from a T to C substitution at nucleotide position 1673. The methionine at codon 558 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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