ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.686C>A (p.Ala229Asp) (rs971190119)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756084 SCV000883800 uncertain significance Hereditary hemorrhagic telangiectasia type 1 2019-12-10 criteria provided, single submitter clinical testing The ENG c.686C>A; p.Ala229Asp variant (rs971190119), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The alanine at codon 229 is not highly conserved, and computational analyses (SIFT, Align GVGD, MutationTaster) predict that this variant is tolerated. Additionally, our laboratory has identified this variant in an individual who also carries a confirmed ENG pathogenic variant on the same allele. However, due to limited information, the clinical significance of the p.Ala229Asp variant is uncertain at this time.
Invitae RCV001342874 SCV001536822 uncertain significance Hereditary hemorrhagic telangiectasia 2020-09-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 229 of the ENG protein (p.Ala229Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ENG-related conditions. ClinVar contains an entry for this variant (Variation ID: 618088). 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. 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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