ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.1594G>T (p.Gly532Cys)

gnomAD frequency: 0.00004  dbSNP: rs587780843
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000123383 SCV000166707 benign Multiple endocrine neoplasia, type 1 2024-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000572942 SCV000673642 likely benign Hereditary cancer-predisposing syndrome 2022-05-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics RCV000123383 SCV000838450 likely benign Multiple endocrine neoplasia, type 1 2024-04-09 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000572942 SCV002530058 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-04 criteria provided, single submitter curation
Baylor Genetics RCV000123383 SCV004194428 uncertain significance Multiple endocrine neoplasia, type 1 2024-02-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000123383 SCV004836524 uncertain significance Multiple endocrine neoplasia, type 1 2024-09-27 criteria provided, single submitter clinical testing This missense variant replaces glycine with cysteine at codon 532 of the MEN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been detected in a family affected with primary hyperparathyroidism and adrenal tumors (PMID: 11836268, 12112656). This variant has been identified in 3/250106 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004589612 SCV005081426 uncertain significance not provided 2023-12-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a single family with features of Multiple Endocrine Neoplasia type 1 (PMID: 12112656); This variant is associated with the following publications: (PMID: 15281352, 10612827, 30869828, 12112656, 11836268, 34326862)
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000123383 SCV005689118 uncertain significance Multiple endocrine neoplasia, type 1 2024-10-19 criteria provided, single submitter clinical testing The MEN1 c.1594G>T (p.Gly532Cys) missense change has a maximum population frequency of 0.003% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). Computational prediction is inconclusive regarding the impact of this variant on protein structure and function; to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in a family with primary hyperparathyroidism and adrenal tumors (PMID: 12112656). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV004748592 SCV005361205 uncertain significance MEN1-related disorder 2024-06-27 no assertion criteria provided clinical testing The MEN1 c.1609G>T variant is predicted to result in the amino acid substitution p.Gly537Cys. This variant has been reported in patients with features consistent with multiple endocrine neoplasia type 1 (Wautot et al. 2002. PMID: 12112656, referred to as p.Gly532Cys in Family 99). This variant was also reported in an individual with breast cancer (Table S4. Bhai P. et al. 2021. PubMed ID: 34326862, referred to as p.Gly532Cys in patient 2447). This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is present in the ClinVar database with interpretation ranging from likely benign to uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/136167/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.