ClinVar Miner

Submissions for variant NM_001077401.2(ACVRL1):c.1450C>T (p.Arg484Trp) (rs121909288)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507762 SCV000602426 pathogenic not specified 2016-12-08 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000008740 SCV000996066 pathogenic Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia 2017-07-19 criteria provided, single submitter clinical testing This missense variant is found in exon 10 of the ACVRL1 gene. This variant, as well as another pathogenic variant at the same amino acid position, are well reported in the literature. The p.Arg484Trp variant has been reported in at least five cases from three independent families in the literature in patients with HHT (PMID: 11484689, 15024723, 27316748). Functional studies have shown that the p.Arg484Trp variant, which lies in the intracellular kinase domain, negatively affects trafficking in the endoplasmic reticulum in HHT patients (PMID: 23124896). The variant is not found in any allele frequency databases. Thus, it is presumed to be rare. Based on the available evidence, this variant is classified as pathogenic.
OMIM RCV000008739 SCV000028948 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2001-08-02 no assertion criteria provided literature only
OMIM RCV000008740 SCV000028949 pathogenic Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia 2001-08-02 no assertion criteria provided literature only
Medical & Molecular Genetics Group,University of Lincoln RCV000008740 SCV000576347 pathogenic Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia no assertion criteria provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003756 SCV001162199 likely pathogenic Pulmonary arterial hypertension no assertion criteria provided research
GeneDx RCV001564363 SCV001787519 pathogenic not provided 2019-04-05 no assertion criteria provided clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Published functional studies demonstrate a damaging effect and suggest functional haploinsufficiency as the mechanism of disease (Ricard et al., 2010; Piao et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 8252; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 32581362, 32503579, 31019026, 27587546, 31727138, 30578383, 29650961, 29743074, 27316748, 30303062, 17786384, 14684682, 16540754, 16690726, 11484689, 12114496, 16429404, 15879500, 18285823, 15517393, 15024723, 16282348, 25970827, 18673552, 26387786, 15266205, 23124896, 20501893, 29449337)

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