ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.1220G>A (p.Ser407Asn) (rs1554809516)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538066 SCV000629549 likely pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-18 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 407 of the ENG protein (p.Ser407Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hereditary hemorrhagic telangiectasia and to segregate with the disease in one family (PMID: 11440987, 16542389 , 16690726 , 22991266). Experimental studies using activated monocytes isolated from a carrier individual indicate that this variant leads to a defect in the maturation of the ENG protein and its traffic to the cell membrane. However, transient over-expression experiments using HeLa cells in culture show that it does not interfere with protein transport into the cell membrane in that system (PMID: 22022569). The clinical relevance of these findings 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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