ClinVar Miner

Submissions for variant NM_003361.4(UMOD):c.326T>A (p.Val109Glu)

gnomAD frequency: 0.00001  dbSNP: rs780462125
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000681768 SCV001446847 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000681768 SCV002231057 uncertain significance not provided 2022-09-12 criteria provided, single submitter clinical testing 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on UMOD protein function. ClinVar contains an entry for this variant (Variation ID: 562322). This missense change has been observed in individual(s) with autosomal dominant medullary cystic kidney disease (PMID: 23988501). This variant is present in population databases (rs780462125, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 109 of the UMOD protein (p.Val109Glu). Experimental studies have shown that this missense change affects UMOD function (PMID: 23988501). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002294367 SCV002587216 uncertain significance Kidney disorder 2016-12-12 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV003336129 SCV004046134 likely pathogenic UMOD-related disorder criteria provided, single submitter clinical testing This variant has been previously reported as a heterozygous change in patients with kidney disease (PMID: 23988501, 30586318, 33574344). Functional analysis showed that the c.326T>A (p.Val109Glu) variant alters the function of the UMOD protein (PMID: 23988501). The c.326T>A (p.Val109Glu) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.001% (3/215296) and thus is presumed to be rare. The c.326T>A (p.Val109Glu) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.326T>A (p.Val109Glu) variant is classified as Likely Pathogenic.
Gharavi Laboratory, Columbia University RCV000681768 SCV000809229 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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