Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000473695 | SCV000552414 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2021-05-25 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Asn335 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 20414677, 32300199), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with hereditary hemorrhagic telangiectasia (HHT) (Invitae). ClinVar contains an entry for this variant (Variation ID: 411313). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with isoleucine at codon 335 of the ACVRL1 protein (p.Asn335Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine. |