Submissions for variant NM_000209.4(PDX1):c.418G>A (p.Ala140Thr)

gnomAD frequency: 0.00022  dbSNP: rs143517122

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000712001	SCV000842414	likely benign	not provided	2020-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000712001	SCV001826082	likely benign	not provided	2021-04-28	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 10720084, 21569088, 15001545)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464032	SCV002605249	benign	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 rs143517122, yet.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000712001	SCV003259033	uncertain significance	not provided	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 140 of the PDX1 protein (p.Ala140Thr). This variant is present in population databases (rs143517122, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of PDX1-related conditions (PMID: 10720084, 21569088). ClinVar contains an entry for this variant (Variation ID: 586036). 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%. Experimental studies have shown that this missense change affects PDX1 function (PMID: 15001545). 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000712001	SCV002035688	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000712001	SCV002038062	likely benign	not provided		no assertion criteria provided	clinical testing