Submissions for variant NM_000384.3(APOB):c.895T>G (p.Phe299Val)

gnomAD frequency: 0.00051  dbSNP: rs72653060

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001838076	SCV001667365	likely benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-01-22	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000655182	SCV001713969	uncertain significance	not provided	2019-08-26	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000655182	SCV002048463	uncertain significance	not provided	2021-05-12	criteria provided, single submitter	clinical testing	The APOB c.895T>G; p.Phe299Val variant (rs72653060), to our knowledge, has not been reported in the medical literature or gene specific databases. This variant is found in the general population with an allele frequency in African populations of 0.16% (41/24,970 alleles) in the Genome Aggregation Database. The phenylalanine at codon 299 is weakly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.213). Based on the available information, the clinical significance of this variant is uncertain.
Ambry Genetics	RCV002369774	SCV002683992	likely benign	Cardiovascular phenotype	2022-06-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000655182	SCV004219833	uncertain significance	not provided	2023-05-19	criteria provided, single submitter	clinical testing	In the published literature, this variant has been reported in an individual with elevated max LDL cholesterol (PMID: 31106297 (2018)) and in an individual with HELLP syndrome (PMID: 33059327 (2020)). The frequency of this variant in the general population, 0.0016 (41/24970 chromosomes in African/African American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences	RCV003918093	SCV004733113	uncertain significance	APOB-related condition	2023-11-29	criteria provided, single submitter	clinical testing	The APOB c.895T>G variant is predicted to result in the amino acid substitution p.Phe299Val. This variant has been reported in the heterozygous state in an individual with HELLP syndrome (Jiménez et al. 2020. PubMed ID: 33059327). This variant is reported in 0.16% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.