ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.1873C>G (p.Gln625Glu) (rs147188969)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001201352 SCV000828407 uncertain significance Hereditary hemorrhagic telangiectasia 2020-05-27 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 625 of the ENG protein (p.Gln625Glu). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ENG-related conditions. ClinVar contains an entry for this variant (Variation ID: 577031). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
Johns Hopkins Genomics, Johns Hopkins University RCV000699684 SCV001167230 uncertain significance Hereditary hemorrhagic telangiectasia type 1 2019-10-14 criteria provided, single submitter clinical testing This ENG variant (rs147188969) is rare (<0.1%) in a large population dataset (gnomAD: 10/237498 total alleles; 0.004211%; no homozygotes). A single submitter in ClinVar classifies this variant as uncertain and p.Gln625Glu has not been reported in the literature to our knowledge. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be benign. The glutamine residue at this position is evolutionarily conserved across some species, but not all. Due to lack of segregation and functional data, we consider the clinical significance of c.1873C>G to be uncertain at this time.

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