ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.1129G>A (p.Ala377Thr)

dbSNP: rs1565594969
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000697373 SCV000825979 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2022-02-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 377 of the ACVRL1 protein (p.Ala377Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 16470589; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 575214). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACVRL1 protein function. Experimental studies have shown that this missense change affects ACVRL1 function (PMID: 16470589). This variant disrupts the p.Arg377 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 23805858), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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