ClinVar Miner

Submissions for variant NM_001104631.2(PDE4D):c.1762A>G (p.Met588Val)

dbSNP: rs1554033934
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000504451 SCV000596384 pathogenic Acrodysostosis 2 with or without hormone resistance 2017-06-20 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000585454 SCV000693171 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000585454 SCV001832426 uncertain significance not provided 2019-11-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000585454 SCV002307723 pathogenic not provided 2023-07-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt PDE4D protein function. ClinVar contains an entry for this variant (Variation ID: 436281). This missense change has been observed in individual(s) with clinical features of acrodysostosis (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 588 of the PDE4D protein (p.Met588Val).
GeneDx RCV000585454 SCV005333504 likely pathogenic not provided 2024-03-01 criteria provided, single submitter clinical testing Identified in a patient with a suspected skeletal dysplasia in the published literature, however, additional clinical information was not provided (PMID: 34627339); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35982159, 33057194, 31785789, 34627339)

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