Total submissions: 5
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, |
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, |
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 |
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, |
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. |