ClinVar Miner

Submissions for variant NM_000209.4(PDX1):c.101C>T (p.Ala34Val)

dbSNP: rs750219172
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001817577 SCV002068910 uncertain significance not specified 2021-12-01 criteria provided, single submitter clinical testing 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 0.045% in the Latino/Admixed American subpopulation (dbSNP rs750219172). The p.Ala34Val change affects a moderately conserved amino acid residue located in a domain of the PDX1 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ala34Val substitution. Due to insufficient evidence and the lack of functional studies, the clinical significance of the p.Ala34Val change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV003728021 SCV004536871 uncertain significance not provided 2024-07-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 34 of the PDX1 protein (p.Ala34Val). This variant is present in population databases (rs750219172, gnomAD 0.05%). 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: 1336622). 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 RCV005006072 SCV005634352 uncertain significance Maturity-onset diabetes of the young type 4; Pancreatic agenesis 1; Type 2 diabetes mellitus 2024-04-23 criteria provided, single submitter clinical testing

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