ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1031G>T (p.Cys344Phe) (rs28936688)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000815009 SCV000955449 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 344 of the ACVRL1 protein (p.Cys344Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hereditary haemorrhagic telangiectasia or clinical features of this disease (PMID: 12114496, Invitae). Experimental studies have shown that this missense variant showed improper cellular localization (PMID: 23124896). This variant disrupts the p.Cys344 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 16470787, 18673552, 16752392, 19767588, 10767348, 15880681), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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