ClinVar Miner

Submissions for variant NM_000209.4(PDX1):c.8G>C (p.Gly3Ala)

gnomAD frequency: 0.00002  dbSNP: rs1380564366
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000712004 SCV000842417 uncertain significance not provided 2022-01-19 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002463733 SCV002605230 uncertain significance Pancreatic hypoplasia criteria provided, single submitter research Potent homozygous mutations in the PDX1 gene can lead to pancreatic agenesis/pancreatic hypoplasia and neonatal diabetes mellitus. However no sufficient evidence is found to ascertain the role of this particular variant rs1380564366 , yet.
Fulgent Genetics, Fulgent Genetics RCV002493262 SCV002779206 uncertain significance Maturity-onset diabetes of the young type 4; Pancreatic agenesis 1; Type 2 diabetes mellitus 2022-03-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000712004 SCV004374266 uncertain significance not provided 2023-06-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 3 of the PDX1 protein (p.Gly3Ala). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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. 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 not expected to disrupt PDX1 protein function. ClinVar contains an entry for this variant (Variation ID: 586037). This missense change has been observed in individual(s) with type 2 diabetes mellitus (PMID: 21569088).
Genetic Services Laboratory, University of Chicago RCV003151139 SCV003839827 uncertain significance not specified 2022-07-14 no assertion criteria provided clinical testing DNA sequence analysis of the PDX1 gene demonstrated a sequence change, c.8G>C, in exon 1 that results in an amino acid change, p.Gly3Ala. This sequence change does not appear to have been previously described in individuals with PDX1-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.039% in the non-Finnish European subpopulation, and 0.0096% in the overall population (dbSNP rs1380564366). The p.Gly3Ala change affects a moderately conserved amino acid residue located in a domain of the PDX1 protein that is not known to be functional. The p.Gly3Ala substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Gly3Ala change remains unknown at this time.

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.