ClinVar Miner

Submissions for variant NM_000209.4(PDX1):c.211C>A (p.Pro71Thr)

gnomAD frequency: 0.00041  dbSNP: rs564129447
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001347094 SCV001541339 uncertain significance not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 71 of the PDX1 protein (p.Pro71Thr). This variant is present in population databases (rs564129447, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with PDX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043044). 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 RCV002499697 SCV002797025 uncertain significance Maturity-onset diabetes of the young type 4; Pancreatic agenesis 1; Type 2 diabetes mellitus 2022-03-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004548190 SCV004119979 uncertain significance PDX1-related disorder 2023-03-10 criteria provided, single submitter clinical testing The PDX1 c.211C>A variant is predicted to result in the amino acid substitution p.Pro71Thr. This variant was reported in an individual tested for dyslipidemias (Table S3/4 - Dron et al. 2020. PubMed ID: 32041611). This variant is reported in 0.16% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-28494486-C-A). Although we suspect this variant could be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004036511 SCV005033400 uncertain significance Maturity onset diabetes mellitus in young 2023-10-31 criteria provided, single submitter clinical testing The p.P71T variant (also known as c.211C>A), located in coding exon 1 of the PDX1 gene, results from a C to A substitution at nucleotide position 211. The proline at codon 71 is replaced by threonine, an amino acid with highly similar properties. This alteration has been reported in multiple unrelated non-diabetic individuals (Flannick J et al. Nat Genet, 2013 Nov;45:1380-5). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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