ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.150G>T (p.Trp50Cys) (rs121909285)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000008730 SCV000552415 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 50 of the ACVRL1 protein (p.Trp50Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (rs121909285, ExAC no frequency). This variant has been reported in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 9245985, 12843319, Invitae database). ClinVar contains an entry for this variant (Variation ID: 8246). Experimental studies have shown that this missense change leads to deficient ACVRL1-related signaling and improper protein trafficking (PMID: 10187774, 14684682). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001557555 SCV001779333 pathogenic not provided 2021-02-26 criteria provided, single submitter clinical testing Segregates with disease in affected individuals from a single family in the published literature (Abdalla et al., 2003); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate mis-localization and impaired protein activity (Lux et al., 1999; Harrison et al., 2003); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#8246; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 16611099, 15266205, 22718755, 17576210, 10767348, 10694922, 12843319, 14684682, 10187774, 9245985, 22028876)
OMIM RCV000008730 SCV000028939 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 1997-07-01 no assertion criteria provided literature only

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