Submissions for variant NM_022437.3(ABCG8):c.1117T>C (p.Cys373Arg)

gnomAD frequency: 0.00001  dbSNP: rs554680915

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000333238	SCV000430518	uncertain significance	Sitosterolemia 1	2018-01-12	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.
Eurofins Ntd Llc (ga)	RCV000595016	SCV000708377	benign	not specified	2017-05-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436203	SCV002752641	uncertain significance	Cardiovascular phenotype	2023-12-03	criteria provided, single submitter	clinical testing	The p.C373R variant (also known as c.1117T>C), located in coding exon 7 of the ABCG8 gene, results from a T to C substitution at nucleotide position 1117. The cysteine at codon 373 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002519974	SCV003287936	likely benign	not provided	2025-01-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000595016	SCV005381409	likely benign	not specified	2025-03-17	criteria provided, single submitter	clinical testing	Variant summary: ABCG8 c.1117T>C (p.Cys373Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00045 in 251274 control chromosomes, predominantly at a frequency of 0.0035 within the South Asian subpopulation in the gnomAD database. To our knowledge, no occurrence of c.1117T>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: 336075). Based on the evidence outlined above, the variant was classified as likely benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV002519974	SCV005411693	uncertain significance	not provided	2024-01-10	criteria provided, single submitter	clinical testing	BP4, PM1_supporting
PreventionGenetics, part of Exact Sciences	RCV003950162	SCV004757894	likely benign	ABCG8-related disorder	2022-06-14	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).