Submissions for variant NM_003661.4(APOL1):c.1152T>G (p.Ile384Met)

gnomAD frequency: 0.06710  dbSNP: rs60910145

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154652	SCV000204328	risk factor	Hyalinosis, Segmental Glomerular	2020-03-04	criteria provided, single submitter	clinical testing	See compound allele p.[Ser342Gly; Ile384Met]
Invitae	RCV001519785	SCV001728717	benign	not provided	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001519785	SCV001982061	benign	not provided	2019-02-08	criteria provided, single submitter	clinical testing	The G1 allele comprises two single nucleotide polymorphisms (c.[1024A>G;1152T>G], p.[Ser342Gly;Ile384Met]), however, the risk associated with the G1 allele is considered to be due to only the c.1024A>G, p.Ser342Gly variant (Kopp et al., 2011). The other polymorphism (c.1152T>G, p.Ile384Met) associated with the G1 allele does not confer an increased risk in isolation (Kruzel-Davila et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32581362, 27650483, 30173819, 28696248, 20647424, 20635188, 24206458, 22832513, 25993319, 24518129, 23768513, 24379297)
Mendelics	RCV002247497	SCV002517868	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Washington University in St. Louis	RCV003458344	SCV004176971	uncertain significance	APOL1-associated kidney disease	2023-08-29	criteria provided, single submitter	clinical testing	Sequence analysis identified the presence of a single APOL1 risk allele in a heterozygous state (G1). The G1 allele is composed of two missense variants: G1G (p.S342G) and G1M (p.I384M). APOL1 risk alleles occur at high frequency among populations of African ancestry (22-24% and 13-14% for G1 and G2, respectively) and are absent or nearly absent from other populations. Inheriting two risk variants greatly increases risk of kidney disease, whereas inheriting one risk allele confers minimal or no risk (Friedman DJ et al., PMID: 32616495). APOL1-associated kidney disease includes focal segmental glomerulosclerosis, CKD associated with hypertension, HIV, systemic lupus erythematosus (SLE), and sickle cell disease, among others (Friedman DJ et al., PMID: 32616495).
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003832	SCV001162283	pathogenic	Proteinuria		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003833	SCV001162284	pathogenic	Focal segmental glomerulosclerosis		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003834	SCV001162285	pathogenic	Focal segmental glomerulosclerosis; Steroid-resistant nephrotic syndrome		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003835	SCV001162286	pathogenic	Focal segmental glomerulosclerosis; Sickled erythrocytes		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003836	SCV001162287	pathogenic	Glomerulonephritis		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003837	SCV001162288	pathogenic	Nephrotic range proteinuria		no assertion criteria provided	research