Submissions for variant NM_022437.3(ABCG8):c.965-1G>C

dbSNP: rs957176669

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000658014	SCV000779785	pathogenic	not provided	2020-04-20	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28739549, 29174072, 32088153)
Eurofins Ntd Llc (ga)	RCV000658014	SCV000859421	pathogenic	not provided	2018-01-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001784224	SCV002019798	pathogenic	Sitosterolemia 1	2023-08-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000658014	SCV002231820	pathogenic	not provided	2022-02-10	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 6 of the ABCG8 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ABCG8 are known to be pathogenic (PMID: 11452359, 15375183, 16029460). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 546173). Disruption of this splice site has been observed in individual(s) with ABCG8-related conditions (PMID: 28739549, 32088153, 32166861). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%).
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001784224	SCV002818186	pathogenic	Sitosterolemia 1	2024-10-04	criteria provided, single submitter	research	PVS1, PM2, PM5
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001784224	SCV005038834	pathogenic	Sitosterolemia 1	2024-03-14	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000658014	SCV001922605	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000658014	SCV001959643	likely pathogenic	not provided		no assertion criteria provided	clinical testing