ClinVar Miner

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

dbSNP: rs137854450
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Total submissions: 8
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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
Labcorp Genetics (formerly Invitae), Labcorp RCV001794457 SCV000823044 pathogenic Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant 2024-12-02 criteria provided, single submitter clinical testing 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). This variant is not present in population databases (gnomAD no frequency). 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 also known as p.Ser97Leu. ClinVar contains an entry for this variant (Variation ID: 16745). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ELANE function (PMID: 16551967, 26567890). 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
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000018229 SCV005328357 pathogenic Neutropenia, severe congenital, 1, autosomal dominant 2024-09-25 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 pathogenic Neutropenia, severe congenital, 1, autosomal dominant 2024-06-12 no assertion criteria provided curation
GeneReviews RCV000990116 SCV002769685 not provided Cyclical neutropenia no assertion provided literature only
PreventionGenetics, part of Exact Sciences RCV004752711 SCV005360939 pathogenic ELANE-related disorder 2024-08-01 no assertion criteria provided clinical testing The ELANE c.377C>T variant is predicted to result in the amino acid substitution p.Ser126Leu. This variant is also described using legacy nomenclature as p.Ser97Leu, has been reported in multiple individuals with congenital neutropenia (Dale et al. 2000. PubMed ID: 11001877; Sera et al. 2005. PubMed ID: 16079102; Newburger et al. 2010. PubMed ID: 20582973; Wali et al. 2012. PubMed ID: 22758217; Gong et al. 2018. PubMed ID: 30386760). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.

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