ClinVar Miner

Submissions for variant NM_014225.6(PPP2R1A):c.547C>T (p.Arg183Trp)

dbSNP: rs1057519946
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000761600 SCV000891763 likely pathogenic Houge-Janssens syndrome 2 2018-04-18 criteria provided, single submitter research ACMG codes: PS2, PM2, PP3
Baylor Genetics RCV000761600 SCV001526406 likely pathogenic Houge-Janssens syndrome 2 2018-12-21 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. A nearby de novo missense variant c.544C>T(p.R182W) had been reported in 3 unrelated individuals with clinical features including hypoplasia or agenesis of corpus callosum, hypotonia and intellectual disability[PMID: 26168268]
GeneDx RCV003318575 SCV004023128 pathogenic not provided 2023-01-27 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (impaired subunit binding) (PMID: 33106617); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34930662, 33106617)
Labcorp Genetics (formerly Invitae), Labcorp RCV003318575 SCV004375018 pathogenic not provided 2023-08-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg183 amino acid residue in PPP2R1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects PPP2R1A function (PMID: 33106617). 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 PPP2R1A protein function. ClinVar contains an entry for this variant (Variation ID: 376505). This missense change has been observed in individual(s) with PPP2R1A-related conditions (PMID: 33106617, 34930662). 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 arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 183 of the PPP2R1A protein (p.Arg183Trp).
GenomeConnect - Brain Gene Registry RCV000761600 SCV004804561 not provided Houge-Janssens syndrome 2 no assertion provided phenotyping only Variant classified as Pathogenic and reported on 05-31-2023 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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