ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.422A>G (p.Gln141Arg)

dbSNP: rs758846538
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001323222 SCV001514130 likely pathogenic Multiple endocrine neoplasia, type 1 2024-09-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 141 of the MEN1 protein (p.Gln141Arg). This variant is present in population databases (rs758846538, gnomAD 0.0009%). This missense change has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 37484956). ClinVar contains an entry for this variant (Variation ID: 1023209). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects MEN1 function (PMID: 35941657). This variant disrupts the p.Gln141 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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