Submissions for variant NM_207352.4(CYP4V2):c.1169G>A (p.Arg390His)

dbSNP: rs199476201

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001358595	SCV002237194	pathogenic	not provided	2024-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 390 of the CYP4V2 protein (p.Arg390His). This variant is present in population databases (rs199476201, gnomAD 0.01%). This missense change has been observed in individual(s) with Bietti crystalline corneoretinal dystrophy (PMID: 21565171, 33090715). ClinVar contains an entry for this variant (Variation ID: 39251). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CYP4V2 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg390 amino acid residue in CYP4V2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22087103, 26971461, 28051075). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
SingHealth Duke-NUS Institute of Precision Medicine	RCV000032528	SCV005881611	pathogenic	Bietti crystalline corneoretinal dystrophy	2025-02-05	criteria provided, single submitter	clinical testing	Variant is located in a mutational hotspot where >50% of variants are pathogenic (PM1). Variant is not found in gnomAD genomes and homozygous allele count in gnomAD exomes is less than 0 (PM2). Other variants at this amino acid residue have been classified as pathogenic/likely pathogenic (PM5, p.Arg390Leu; p.Arg390Cys). REVEL score is 0.96 (PP3_str). Variant is found to be in trans with another pathogenic variant (PM3)
GeneReviews	RCV000032528	SCV000056191	pathologic	Bietti crystalline corneoretinal dystrophy	2012-04-12	no assertion criteria provided	curation	Converted during submission to Pathogenic.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358595	SCV001554381	uncertain significance	not provided		no assertion criteria provided	clinical testing