Submissions for variant NM_022437.3(ABCG8):c.1386C>T (p.Asn462=)

gnomAD frequency: 0.00008  dbSNP: rs371163697

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000888273	SCV001031899	likely benign	not provided	2024-01-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000888273	SCV001249223	likely benign	not provided	2022-04-01	criteria provided, single submitter	clinical testing	ABCG8: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001139359	SCV001299501	uncertain significance	Sitosterolemia 1	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.
Ambry Genetics	RCV002390870	SCV002702612	likely benign	Cardiovascular phenotype	2019-10-26	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.
New York Genome Center	RCV001139359	SCV003925254	uncertain significance	Sitosterolemia 1	2022-03-17	criteria provided, single submitter	clinical testing	The c.1386C>T (p.Asn462=) variant identified in the ABCG8 gene is a synonymous variant that does not result in a change of amino acid at the moderately conserved p.Asn462 residue (exon 9/13). This variant is found in gnomAD(v2.1) (101 heterozygotes, 1 homozygote; allele frequency: 3.572e-4),and reported in ClinVar as both Likely Benign (n=1) and a Variant of Uncertain Significance (n=2) (VarID:715758). To our current knowledge, the c.1386C>T (p.Asn462=) variant has not been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity, the c.1386C>T(p.Asn462=) variant identified in the ABCG8 gene is reported as Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV003948394	SCV004773682	likely benign	ABCG8-related condition	2020-02-14	criteria provided, single submitter	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).