Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069381 | SCV001234545 | uncertain significance | Hereditary hemorrhagic telangiectasia | 2019-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 587 of the ENG protein (p.Leu587Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs747196026, ExAC 0.002%). This variant has been observed in an individual affected with hereditary hemorrhagic telangiectasia that also carried a pathogenic variant in ACVRL1 (p.Arg411Trp) which was suggested to be the primary cause of disease (PMID: 25312062). This variant has been reported in an individual affected with intracranial aneurysm (PMID: 19299629). This variant has been reported not to substantially affect ENG protein function (PMID: 25312062). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Illumina Laboratory Services, |
RCV001166476 | SCV001328857 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |