ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.1319T>G (p.Val440Gly) (rs1554809363)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633145 SCV000754359 uncertain significance Hereditary hemorrhagic telangiectasia 2019-02-11 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 440 of the ENG protein (p.Val440Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with hereditary hemorraghic telangiectasia (HHT) in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 528065). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285345 SCV001471759 uncertain significance Hereditary hemorrhagic telangiectasia type 1 2020-03-12 criteria provided, single submitter clinical testing The ENG c.1319T>G; p.Val440Gly variant, to our knowledge, is not reported in the medical literature but is reported in the ClinVar database (Variation ID: 528065). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The valine at codon 440 is a moderately conserved residue in the zona pellucida domain, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, a different variant at this codon (p.Val440Met) is reported in the HHT variant database (see link). However, due to limited information, the clinical significance of the p.Val440Gly variant is uncertain at this time. REFERENCES ENG HHT database link: https://arup.utah.edu/database/ENG/ENG_display.php

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