ClinVar Miner

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

dbSNP: rs137854450
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Total submissions: 6
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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 RCV001794457 SCV000823044 pathogenic Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant 2023-06-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ELANE function (PMID: 16551967, 26567890). 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 ELANE protein function. ClinVar contains an entry for this variant (Variation ID: 16745). This variant is also known as p.Ser97Leu. This missense change has been observed in individuals with cyclic neutropenia and severe congenital neutropenia (PMID: 11001877, 14962902, 16079102, 16737875, 18611981, 20582973, 22758217, 23463630). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 126 of the ELANE protein (p.Ser126Leu).
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, Sultan Qaboos University RCV000018229 SCV000891498 uncertain significance Neutropenia, severe congenital, 1, autosomal dominant 2017-12-30 no assertion criteria provided curation
GeneReviews RCV000990116 SCV002769685 not provided Cyclical neutropenia no assertion provided literature only

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