Submissions for variant NM_001106.4(ACVR2B):c.1147C>T (p.Arg383Cys)

dbSNP: rs1559655653

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000754875	SCV001577623	likely pathogenic	Heterotaxy, visceral, 4, autosomal	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 383 of the ACVR2B protein (p.Arg383Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with laterality defects (PMID: 30622330). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 545541). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Baylor Genetics	RCV000754875	SCV003835860	likely pathogenic	Heterotaxy, visceral, 4, autosomal	2022-10-14	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000754875	SCV000778472	uncertain significance	Heterotaxy, visceral, 4, autosomal	2018-05-28	no assertion criteria provided	research