ClinVar Miner

Submissions for variant NM_001972.4(ELANE):c.377C>T (p.Ser126Leu) (rs137854450)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000508432 SCV000603440 pathogenic not specified 2016-12-21 criteria provided, single submitter clinical testing
Invitae RCV000694593 SCV000823044 pathogenic Cyclical neutropenia; Neutropenia, severe congenital 1, autosomal dominant 2020-10-19 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 126 of the ELANE protein (p.Ser126Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with cyclic neutropenia and severe congenital neutropenia (PMID: 14962902, 18611981, 23463630, 22758217, 11001877, 16079102). Also, this variant segregates with cyclic neutropenia and severe congenital neutropenia in one family (PMID: 20582973, 16737875). This variant is also known as p.Ser97Leu in the literature. ClinVar contains an entry for this variant (Variation ID: 16745). Experimental studies have shown that this missense change alone does not affect the ELANE protein function. However, in combination with knockdown of secretory leucocyte protease inhibitor (SLPI), a natural ELANE inhibitor, this variant may impair the ELANE protein function (PMID: 26567890, 16551967). The clinical significance of these findings is uncertain. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000990116 SCV001140921 pathogenic Cyclical neutropenia 2019-05-28 criteria provided, single submitter clinical testing
OMIM RCV000018229 SCV000038508 pathogenic Neutropenia, severe congenital 1, autosomal dominant 2008-01-01 no assertion criteria provided literature only
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000018229 SCV000891498 uncertain significance Neutropenia, severe congenital 1, autosomal dominant 2017-12-30 no assertion criteria provided curation

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