Submissions for variant NM_003560.4(PLA2G6):c.901C>T (p.Arg301Cys)

gnomAD frequency: 0.00006  dbSNP: rs367854265

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000997930	SCV001153703	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing	PLA2G6: PM5
GeneDx	RCV000997930	SCV001780745	uncertain significance	not provided	2021-01-05	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32771225, 30065071, 23182313, 22213678, 21368765)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858869	SCV002270991	uncertain significance	Infantile neuroaxonal dystrophy	2022-10-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 301 of the PLA2G6 protein (p.Arg301Cys). This variant is present in population databases (rs367854265, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of PLA2G6-related conditions (PMID: 21368765, 32771225). ClinVar contains an entry for this variant (Variation ID: 809369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Fulgent Genetics, Fulgent Genetics	RCV002481790	SCV002775434	uncertain significance	Infantile neuroaxonal dystrophy; Neurodegeneration with brain iron accumulation 2B; Autosomal recessive Parkinson disease 14	2021-08-17	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000997930	SCV001742666	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000997930	SCV001964548	uncertain significance	not provided		no assertion criteria provided	clinical testing