ClinVar Miner

Submissions for variant NM_000939.4(POMC):c.394C>G (p.Pro132Ala)

dbSNP: rs8192606
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001139997 SCV001300202 uncertain significance Obesity due to pro-opiomelanocortin deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001139998 SCV001300203 uncertain significance Obesity 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV001580566 SCV001817854 uncertain significance not provided 2024-04-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Variant reported in multiple patients with severe obesity but also reported in patients from the control group in the published literature (PMID: 28377240, 16459314, 18091355, 29970488); This variant is associated with the following publications: (PMID: 16459314, 25448875, 18091355, 29970488, 28377240, 35562395)
Genetic Services Laboratory, University of Chicago RCV001819845 SCV002070876 uncertain significance not specified 2019-02-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001580566 SCV002323481 benign not provided 2023-12-11 criteria provided, single submitter clinical testing
Mendelics RCV001819845 SCV002519066 benign not specified 2022-05-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001580566 SCV004138690 likely benign not provided 2022-12-01 criteria provided, single submitter clinical testing POMC: BS2
Clinical Genetics, Academic Medical Center RCV001580566 SCV001922139 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001580566 SCV001930401 likely benign not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538359 SCV004116899 uncertain significance POMC-related disorder 2024-08-08 no assertion criteria provided clinical testing The POMC c.394C>G variant is predicted to result in the amino acid substitution p.Pro132Ala. This variant has been reported in several individuals with obesity (Lee et al. 2006. PubMed ID: 16459314; Table S1, Kleinendorst et al. 2018. PubMed ID: 29970488; Dubern et al. 2008. PubMed ID: 18091355; Shah et al. 2023. PubMed ID: 36864747; Nordang et al. 2017. PubMed ID: 28377240) but also in control subjects (Nordang et al. 2017. PubMed ID: 28377240). In vitro functional studies showed this variant did not reduce protein function and could cause increased function (Supplemental Data Set 3, Shah et al. 2023. PubMed ID: 36864747). This variant is reported in 0.21% of alleles in individuals of European (Finnish) descent in gnomAD, including one homozygous individual. Although we suspect that this variant may be benign, 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.