Submissions for variant NM_022437.3(ABCG8):c.1667T>C (p.Phe556Ser)

gnomAD frequency: 0.00002  dbSNP: rs548098742

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000731839	SCV000859692	uncertain significance	not provided	2018-02-09	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000731839	SCV002541824	uncertain significance	not provided	2021-11-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002507299	SCV002816576	uncertain significance	Gallbladder disease 4; Sitosterolemia 1	2021-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000731839	SCV003258537	benign	not provided	2023-12-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003165977	SCV003912012	likely benign	Cardiovascular phenotype	2022-12-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
New York Genome Center	RCV002245631	SCV003925202	uncertain significance	Sitosterolemia 1	2022-06-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004768618	SCV005380879	likely benign	not specified	2024-08-08	criteria provided, single submitter	clinical testing	Variant summary: ABCG8 c.1667T>C (p.Phe556Ser) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00078 in 251310 control chromosomes, predominantly at a frequency of 0.0062 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is higher than the estimated maximal expected allele frequency for a pathogenic variant in ABCG8 causing Early Onset Coronary Artery Disease phenotype (0.005). To our knowledge, no occurrence of c.1667T>C in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 596119). Based on the evidence outlined above, the variant was classified as likely benign.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245631	SCV002515684	uncertain significance	Sitosterolemia 1		no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV003965531	SCV004789385	likely benign	ABCG8-related disorder	2020-03-06	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).