ClinVar Miner

Submissions for variant NM_000209.4(PDX1):c.296C>A (p.Pro99His)

gnomAD frequency: 0.00013  dbSNP: rs764870332
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001909803 SCV002185654 uncertain significance not provided 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 99 of the PDX1 protein (p.Pro99His). This variant is present in population databases (rs764870332, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Type 2 diabetes and/or healthy controls (PMID: 21569088). ClinVar contains an entry for this variant (Variation ID: 1408111). 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 with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002490245 SCV002800958 uncertain significance Maturity-onset diabetes of the young type 4; Pancreatic agenesis 1; Type 2 diabetes mellitus 2021-11-04 criteria provided, single submitter clinical testing
GeneDx RCV001909803 SCV005333215 uncertain significance not provided 2024-02-02 criteria provided, single submitter clinical testing Reported in a patient with diabetes mellitus type 2 and the control group in published literature (PMID: 21569088); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32041611, 21569088)

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