ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.1416G>C (p.Trp472Cys)

dbSNP: rs1060503243
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000464251 SCV000552410 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2024-04-08 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 472 of the ACVRL1 protein (p.Trp472Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 411309). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002221542 SCV002499026 uncertain significance not provided 2022-04-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV002393155 SCV002699718 uncertain significance Cardiovascular phenotype 2020-11-16 criteria provided, single submitter clinical testing The p.W472C variant (also known as c.1416G>C), located in coding exon 9 of the ACVRL1 gene, results from a G to C substitution at nucleotide position 1416. The tryptophan at codon 472 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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