ClinVar Miner

Submissions for variant NM_007259.5(VPS45):c.671C>A (p.Thr224Asn)

dbSNP: rs879255237
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000049320 SCV002228672 pathogenic Congenital neutropenia-myelofibrosis-nephromegaly syndrome 2023-09-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 224 of the VPS45 protein (p.Thr224Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with severe congenital neutropenia (PMID: 23599270, 23738510). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 55906). 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 expected to disrupt VPS45 protein function. Experimental studies have shown that this missense change affects VPS45 function (PMID: 23599270). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000049320 SCV004238396 pathogenic Congenital neutropenia-myelofibrosis-nephromegaly syndrome 2023-06-19 criteria provided, single submitter clinical testing
OMIM RCV000049320 SCV000081752 pathogenic Congenital neutropenia-myelofibrosis-nephromegaly syndrome 2013-07-04 no assertion criteria provided literature only

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