Submissions for variant NM_000213.5(ITGB4):c.182G>A (p.Cys61Tyr)

gnomAD frequency: 0.00001  dbSNP: rs80338755

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413122	SCV000490569	pathogenic	not provided	2022-07-21	criteria provided, single submitter	clinical testing	Recurrent pathogenic variant commonly seen in Hispanic individuals in the United States with EB-PA (Varki et al., 2006); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 11328943, 9792864, 16473856, 18779879, 20301336)
Biomedical Innovation Departament, CIEMAT	RCV000015855	SCV001547433	pathogenic	Junctional epidermolysis bullosa with pyloric atresia	2016-03-21	criteria provided, single submitter	research
Fulgent Genetics, Fulgent Genetics	RCV002504794	SCV002810464	pathogenic	Junctional epidermolysis bullosa with pyloric atresia; Epidermolysis bullosa, junctional 5A, intermediate	2021-08-05	criteria provided, single submitter	clinical testing
Invitae	RCV000413122	SCV003443311	pathogenic	not provided	2023-12-05	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 61 of the ITGB4 protein (p.Cys61Tyr). This variant is present in population databases (rs80338755, gnomAD 0.003%). This missense change has been observed in individuals with epidermolysis bullosa with pyloric atresia (PMID: 9792864, 16473856). ClinVar contains an entry for this variant (Variation ID: 14734). 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 ITGB4 protein function. For these reasons, this variant has been classified as Pathogenic.
Center for Personalized Medicine, Children's Hospital Los Angeles	RCV003156061	SCV003845223	likely pathogenic	See cases	2022-12-21	criteria provided, single submitter	clinical testing
OMIM	RCV000015855	SCV000036122	pathogenic	Junctional epidermolysis bullosa with pyloric atresia	1998-11-01	no assertion criteria provided	literature only
GeneReviews	RCV000015855	SCV000040554	not provided	Junctional epidermolysis bullosa with pyloric atresia		no assertion provided	literature only