Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV003120157 | SCV003799821 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2022-05-05 | criteria provided, single submitter | clinical testing | The ENG c.579_580delGC; p.Leu194ArgfsTer139 variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with HHT and are considered pathogenic (Bayrak-Toydemir 2006, Bossler 2006, Torring 2014). Based on available information, this variant is classified as pathogenic. References: Bayrak-Toydemir P et al. Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A. 2006 Mar 1;140(5):463-70. Bossler AD et al. Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat. 2006 Jul;27(7):667-75. Torring PM et al. National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet. 2014 Aug;86(2):123-33. |