Submissions for variant NM_000041.4(APOE):c.487C>T (p.Arg163Cys)

gnomAD frequency: 0.00701  dbSNP: rs769455

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000884152	SCV001027508	benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000884152	SCV001836588	benign	not provided	2019-07-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24239320, 26377243, 3243553, 22069485, 20981092, 11500500, 24507774)
H3Africa Consortium	RCV001777143	SCV002014648	benign	not specified	2020-10-28	criteria provided, single submitter	research	While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.069, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error.
Genetic Services Laboratory, University of Chicago	RCV001777143	SCV002065969	benign	not specified	2021-02-15	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV000884152	SCV002503532	uncertain significance	not provided	2020-11-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326680	SCV002633850	benign	Cardiovascular phenotype	2019-09-06	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000884152	SCV005408856	uncertain significance	not provided	2023-10-17	criteria provided, single submitter	clinical testing	BS1, BS2, PS3
OMIM	RCV000019432	SCV000039721	pathogenic	Familial type 3 hyperlipoproteinemia	1988-11-01	no assertion criteria provided	literature only
Reproductive Health Research and Development, BGI Genomics	RCV000019432	SCV001142489	likely pathogenic	Familial type 3 hyperlipoproteinemia	2020-01-06	no assertion criteria provided	curation	NM_000041.2:c.487C>T in the APOE gene has an allele frequency of 0.021 in African subpopulation in the gnomAD database. The p.Arg163Cys (NM_000041.2:c.487C>T) variant has been reported to be associated with type III hyperlipoproteinemia (PMID: 25502880; 26802169). In vitro functional studies suggest that the p.Arg163Cys variant may affect protein function (PMID: 26802169). Pathogenic computational verdict because pathogenic predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, MVP, MutationAssessor, MutationTaster, REVEL and SIFT. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PS3; PP4; PP3.
PreventionGenetics, part of Exact Sciences	RCV003924846	SCV004742648	likely benign	APOE-related disorder	2023-08-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).