ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.23T>C (p.Leu8Pro) (rs1564466414)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000684900 SCV000812361 likely pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-05-17 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 8 of the ENG protein (p.Leu8Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hereditary hemorrhagic telangiectasia in a family and has been reported in individuals with this condition (PMID: 15024723, 19767588). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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