Submissions for variant NM_000282.4(PCCA):c.425G>A (p.Gly142Asp)

dbSNP: rs796052019

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186085	SCV000239109	pathogenic	not provided	2019-09-16	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; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 30014764, 22156789, 27959697, 30274917, 27629047, 30705822, 33101984)
Baylor Genetics	RCV000414788	SCV000328820	pathogenic	Propionic acidemia	2024-03-16	criteria provided, single submitter	clinical testing
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000414788	SCV000996285	pathogenic	Propionic acidemia		criteria provided, single submitter	clinical testing	Compatible metabolite assay
Labcorp Genetics (formerly Invitae), Labcorp	RCV000414788	SCV001401517	pathogenic	Propionic acidemia	2023-06-20	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 142 of the PCCA protein (p.Gly142Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with propionic acidemia (PMID: 22156789, 30705822). ClinVar contains an entry for this variant (Variation ID: 203880). 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 PCCA protein function. This variant disrupts the p.Gly142 amino acid residue in PCCA. Other variant(s) that disrupt this residue have been observed in individuals with PCCA-related conditions (PMID: 30274917), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003984829	SCV004801163	pathogenic	Pontocerebellar hypoplasia type 2D	2024-03-14	criteria provided, single submitter	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000414788	SCV001133014	pathogenic	Propionic acidemia	2019-09-26	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000414788	SCV003927937	pathogenic	Propionic acidemia	2023-04-01	no assertion criteria provided	clinical testing