Submissions for variant NM_022436.3(ABCG5):c.914C>G (p.Thr305Arg)

dbSNP: rs143740796

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001350898	SCV001545326	likely pathogenic	Sitosterolemia	2024-07-23	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 305 of the ABCG5 protein (p.Thr305Arg). This variant is present in population databases (rs143740796, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of dyslipidemia and/or sitosterolemia (PMID: 28696550, 32041611). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1046346). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002280904	SCV002569279	pathogenic	Sitosterolemia 2		criteria provided, single submitter	clinical testing
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245972	SCV002515650	pathogenic	Sitosterolemia 1		no assertion criteria provided	research