Submissions for variant NM_014225.6(PPP2R1A):c.430C>T (p.Arg144Cys)

dbSNP: rs2122329969

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001561105	SCV001783641	pathogenic	not provided	2019-10-13	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001561105	SCV003307405	uncertain significance	not provided	2023-02-11	criteria provided, single submitter	clinical testing	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. 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: 1197324). This variant has not been reported in the literature in individuals affected with PPP2R1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 144 of the PPP2R1A protein (p.Arg144Cys).
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV003336417	SCV004045825	likely pathogenic	Houge-Janssens syndrome 2	2022-12-13	criteria provided, single submitter	clinical testing