Submissions for variant NM_000211.5(ITGB2):c.382G>T (p.Asp128Tyr)

dbSNP: rs137852615

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000087118	SCV004298804	pathogenic	Leukocyte adhesion deficiency 1	2023-05-16	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with leukocyte adhesion deficiency type 1 (LAD1) (PMID: 20549317, 32279896). 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 aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 128 of the ITGB2 protein (p.Asp128Tyr). ClinVar contains an entry for this variant (Variation ID: 68215). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp128 amino acid residue in ITGB2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1590804, 24338230, 26497373; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects ITGB2 function (PMID: 28445705). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ITGB2 protein function.
UniProtKB/Swiss-Prot	RCV000059049	SCV000090570	not provided	not provided		no assertion provided	not provided
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000087118	SCV000119979	pathogenic	Leukocyte adhesion deficiency 1		no assertion criteria provided	not provided	Converted during submission to Pathogenic.