ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1031G>A (p.Cys344Tyr) (rs28936688)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000008742 SCV000552396 pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 344 of the ACVRL1 protein (p.Cys344Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (rs28936688, ExAC no frequency). This variant has been reported in multiple individuals and families affected with hereditary hemorrhagic telangiectasia (PMID: 10767348, 14684682, 15880681, 16540754, 16542389, 17384219, 12114496). ClinVar contains an entry for this variant (Variation ID: 8254). Experimental studies have shown that this missense change causes improper ACVRL1 trafficking and has dominant-negative effects in vitro (PMID: 14684682, 16282348). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000505979 SCV000602410 pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing The ACVRL1 c.1031G>A; p.Cys344Tyr variant (rs28936688) has been reported in several individuals with hereditary hemorrhagic telangiectasia (HHT)(see HHT database link and references therein). This variant has been reported in ClinVar (Variation ID: 8254), and is absent from the general population databases (Exome Variant Server, Genome Aggregation Database). The cysteine at codon 344 is a highly conserved residue located in the protein kinase domain, and computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be damaging to the protein. Taken together, this variant is considered pathogenic. REFERENCES Link to ARUP HHT database: http://arup.utah.edu/database/ACVRL1/ACVRL1_display.php Link to ClinVar database for p.Cys344Tyr: https://www.ncbi.nlm.nih.gov/clinvar/variation/8254/
Baylor Miraca Genetics Laboratories, RCV000008742 SCV000807277 pathogenic Hereditary hemorrhagic telangiectasia type 2 2017-09-01 criteria provided, single submitter clinical testing This mutation has been described in the literature as disease-causing and has been identified once in our laboratory in an individual with HHT; the affected parent was unavailable for testing.
OMIM RCV000008742 SCV000028951 pathogenic Hereditary hemorrhagic telangiectasia type 2 2003-12-01 no assertion criteria provided literature only
OMIM RCV000008743 SCV000028952 pathogenic Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia 2003-12-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.