ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.118G>T (p.Gly40Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001350260 SCV001544648 uncertain significance Hereditary hemorrhagic telangiectasia 2020-08-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 40 of the ENG protein (p.Gly40Cys). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs778319338, ExAC 0.01%). This variant has not been reported in the literature in individuals with ENG-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ENG protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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