Submissions for variant NM_207352.4(CYP4V2):c.1120G>T (p.Asp374Tyr)

gnomAD frequency: 0.00013  dbSNP: rs376015936

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001148838	SCV001309750	uncertain significance	Bietti crystalline corneoretinal dystrophy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001148839	SCV001309751	uncertain significance	Corneal dystrophy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001363608	SCV001559726	uncertain significance	not provided	2023-08-03	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs376015936, gnomAD 0.02%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 374 of the CYP4V2 protein (p.Asp374Tyr). This variant has not been reported in the literature in individuals affected with CYP4V2-related conditions. 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 not expected to disrupt CYP4V2 protein function. ClinVar contains an entry for this variant (Variation ID: 902350).
Ambry Genetics	RCV003163331	SCV003871278	uncertain significance	Inborn genetic diseases	2023-01-24	criteria provided, single submitter	clinical testing	The c.1120G>T (p.D374Y) alteration is located in exon 9 (coding exon 9) of the CYP4V2 gene. This alteration results from a G to T substitution at nucleotide position 1120, causing the aspartic acid (D) at amino acid position 374 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.