Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV001263068 | SCV001441145 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2018-01-01 | criteria provided, single submitter | research | PVS1+PM2+PP4 |
ARUP Laboratories, |
RCV001263068 | SCV002048569 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2021-04-06 | criteria provided, single submitter | clinical testing | The ENG c.1411C>T; p.Gln471Ter variant has been described in individuals with hereditary hemorrhagic telangiectasia (Komiyama 2014, Shovlin 2020). The variant is listed in the ClinVar database (Variation ID: 983198) but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Komiyama M et al. Hereditary hemorrhagic telangiectasia in Japanese patients. J Hum Genet. 2014 Jan;59(1):37-41. PMID: 24196379. Shovlin CL et al. Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. Blood. 2020 Oct 22;136(17):1907-1918. PMID: 32573726. |
Ambry Genetics | RCV002393677 | SCV002701775 | pathogenic | Cardiovascular phenotype | 2016-09-29 | criteria provided, single submitter | clinical testing | The p.Q471* pathogenic mutation (also known as c.1411C>T), located in coding exon 11 of the ENG gene, results from a C to T substitution at nucleotide position 1411. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration was reported in a Japanese family with hereditary hemorrhagic telangiectasia (Komiyama M et al. J. Hum. Genet., 2014 Jan;59:37-41). As such, this alteration is interpreted as a disease-causing mutation. |
Invitae | RCV002537646 | SCV003441485 | pathogenic | Hereditary hemorrhagic telangiectasia | 2022-10-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln471*) in the ENG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 983198). This premature translational stop signal has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 24196379). This variant is not present in population databases (gnomAD no frequency). |